Drugs For Treatment Of Lung Cancer Research Articles

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

Spectroscopic Characterization, Quantum Chemical, Molecular Docking, Antibacterial and Anticancer Studies on Ethyl Coumarin-3-Carboxylate: an Antibacterial and Lung Cancer Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the Ethyl Coumarin-3-Carboxylate (ECC) molecule were carried out. The ECC compound’s pharmacological properties were also investigated, utilizing antibacterial and anticancer activity investigations. Initially, the ECC molecule was optimized by the density functional theory B3LYP method with a 6-311 G++ (d,p) basis set using the Gaussian 09 W program. The optimized molecular structure provides the harmonic vibrational frequencies of the ECC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π →π* and n → π* electronic transitions. The Frontier molecular orbital analysis confirmed the molecular reactivity and bioactivity of ECC, while the Mulliken atomic charge distribution analysis pinpointed the molecule’s reactive sites. Antibacterial testing demonstrated the ECC compound’s inhibitory effect on various bacterial strains, with a particular impact on Klebsiella pneumonia. In vitro, anticancer assessments showcased ECC's stronger inhibitory effects on A549 lung cancer cell lines compared to HeLa cervical cancer cell lines. Additionally, in silico molecular docking investigations provided further validation that the ECC compound can inhibit the function of the epidermal growth factor receptor, a factor associated with lung cancer. As a result, this study lays the foundation for the development of novel drugs for lung cancer treatment.

Effects of the Supercritical Fluid Extract of Magnolia figo on Inducing the Apoptosis of Human Non-Small-Cell Lung Cancer Cells

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography–mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment.

Antitumor activity of bengamide ii in a panel of human and murine tumor cell lines: In vitro and in vivo determination of effectiveness against lung cancer

Lung cancer is the most commonly diagnosed cancer and the one that causes the most deaths worldwide, so there is a need for therapies that improve survival rates. Products derived from marine organisms are a source of novel and potent antitumor compounds, but they present the great obstacle of their obtaining from the natural environment and the problems associated with the synthesis and biological effects of chemical analogues. In this work, a Bengamide analogue (Bengamide II) was chemically synthesized and in vitro and in vivo studies were performed to determine its antitumor activity and mechanisms of action. It was shown to have potent antiproliferative activity in lung cancer lines in 2D and 3D models. In addition, Bengamide II-treated cells showed G2/M and G0/G1 cell cycle arrest, together with a decrease in the proliferation marker Ki67. As for the mechanism of action, the treatment was associated with increased LC3-II expression and production of acidic vesicles signaling autophagy. In addition, Bengamide II treatment was associated with caspase-3 activation and DNA fragmentation related to apoptosis. Furthermore, a reduction of VEGFA expression, related to angiogenesis, was also observed. In vivo studies showed that Bengamide II markedly reduced tumor volume and metastases increasing survival. Additionally, it revealed no systemic toxicity in in vivo models at the therapeutic doses used, which is essential for its future clinical use. Taken together, the chemically synthesized bengamide analogue Bengamide II, is a promising drug for lung cancer treatment showing relevant antitumor activity and significant safety.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.

Impact assessment of expanding the utilization of novel antineoplastic drugs for lung cancer treatment on key performance indicators of the Federal project «Cancer control»

С 2019 г. в Российской Федерации реализуется Федеральный проект «Борьба с онкологическими заболеваниями», основная цель которого – снижение смертности населения от злокачественных новообразований (ЗНО) к 2024 году. Целью исследования является оценка эффектов от расширения применения современных лекарственных препаратов для лечения рака легкого на ключевые показатели Федерального проекта по борьбе с онкозаболеваниями. Материалы и методы. На основе представленной ранее методики оценивались эффекты от расширения практики применения осимертиниба (в первой линии местнораспространенного или метастатического EGFRm+ НМРЛ) и дурвалумаба (в консолидирующей терапии нерезектабельного местнораспространенного НМРЛ после ХЛТ и в первой линии распространенного МРЛ) на показатели смертности и одногодичной летальности. При моделировании общей выживаемости когорт пациентов, получающих варианты сравнения, использовались данные зарубежных клинических исследований и исследований реальной практики применения препаратов. Результаты. Лечение дурвалумабом и осимертинибом по рассматриваемым показаниям в России дополнительно показано 4 053 и 1 596 пациентам ежегодно. Если все они станут получать данные лекарственные препараты смертность от новообразований может быть снижена на 1 682 случая за три года (508 случаев в 2023 году, 644 случая в 2024 году и 531 случай в 2025 году). Расширение практики применения осимертиниба и дурвалумаба в поздних стадиях рака легкого способно снизить одногодичную летальность от всех ЗНО на 0,11 процентных пункта, а среди больных раком легкого – на 1,18 процентных пункта. Выводы. Применение современных противоопухолевых препаратов для лечения рака легкого в разных клинических ситуациях ведет к количественно измеримому вкладу в снижение смертности от ЗНО в России.

Sulfonylated Indeno[1,2-c]quinoline Derivatives as Potent EGFR Tyrosine Kinase Inhibitors.

The epidermal growth factor receptor (EGFR) has been considered a potential target for lung cancer therapy due to its essential role in regulating the survival and proliferation of cancer cells. Although erlotinib, a potent EGFR tyrosine kinase (EGFR-TK) inhibitor, has been used as the first-line drug for lung cancer treatment, acquired drug resistance caused by the T790M secondary mutation of EGFR-TK inevitably develops after a median response duration of 9-13 months. Thus, the search for promising compounds to effectively target EGFR-TK has become an imperative necessity. In this study, the kinase inhibitory activities of a series of sulfonylated indeno[1,2-c]quinolines (SIQs) against EGFR-TK were experimentally and theoretically investigated. Among the 23 SIQ derivatives studied, eight compounds showed enhanced EGFR-TK inhibitory activity (IC50 values of ca. 0.6-10.2 nM) compared to the known drug erlotinib (IC50 of ∼20 nM). In a cell-based assay in human cancer cell lines with EGFR overexpression (A549 and A431 cells), the eight selected SIQs all showed more significant cytotoxicity against A431 than A549 cells, consistent with the higher EGFR expression in A431 cells. Molecular docking and FMO-RIMP2/PCM calculations revealed that SIQ17 occupies the ATP-binding site of EGFR-TK, where its sulfonyl group is mainly stabilized by C797, L718, and E762 residues. Triplicate 500 ns molecular dynamics (MD) simulations also confirmed the binding strength of SIQ17 in complex with EGFR. Overall, the potent SIQ compounds obtained in this work could be further optimized for developing novel anticancer drug candidates targeting EGFR-TK.

Total alkaloids in Stephania tetrandra induce apoptosis by regulating BBC3 in human non–small cell lung cancer cells

PurposeThis study investigated the effects of total alkaloids in Stephania tetrandra (TAS) and the main alkaloid components tetrandrine, fangchinoline and cepharanthine on the biological function of lung cancer cells and the mechanism underlying the synergistic antitumor effects of TAS and cisplatin. MethodsRNA sequencing analysis was performed on TAS-treated H1299 cells. Differentially expressed genes were identified and analyzed, and the regulatory pathway was identified by gene set enrichment analysis. The mRNA and protein expression levels of the differentially expressed genes in cells were determined using quantitative reverse transcription–polymerase chain reaction and western blotting, respectively. Cell viability and wound healing assays evaluated the biological function of TAS and the main alkaloid components in non–small cell lung cancer (NSCLC) cells. Flow cytometry was used to determine the apoptosis rate in NSCLC cells. ResultsTAS inhibited the proliferation and migration of A549 and H1299 cells and increased the apoptosis rate in a time- and dose-dependent manner. When H1299 cells were treated with TAS (7.5 µg/ml), MGLL and BBC3 were identified as the possible differentially expressed genes. Pathways associated with cisplatin resistance were screened to investigate the effect of TAS on the apoptosis of NSCLC cells. TAS may regulate fatty acid metabolism and induce apoptosis through the upregulated expression of MGLL and BBC3. The combination of TAS at noncytotoxic concentrations (A549: 1.0 μg/ml; H1299: 3.0 μg/ml) and cisplatin significantly inhibited the viability of A549 and H1299 cells. ConclusionTAS and the main alkaloid components exert anticancer activity in NSCLC by regulating tumor cell proliferation and apoptosis. Therefore, TAS and the main alkaloid components have the potential to be used as multi-targeted drugs for lung cancer treatment.

Garlic Extract Participates in the Proliferation and Apoptosis of Nonsmall Cell Lung Cancer Cells Via Endoplasmic Reticulum Stress Pathway.

To investigate the effect of garlic extract (GE) on the proliferation and apoptosis of cell lines A549 and H1299 in lung cancer (LC). A549 and H1299 cells with well-developed logarithmic growth were added with GE at a concentration of 0 μg/ml, 25 μg/ml, 50 μg/M, 75 μg/ml, and 100 μg/ml, respectively. The inhibition of A549 cell proliferation was detected using CCK-8 after cultured for 24 h, 48 h, and 72 h. The apoptosis of A549 cells was analyzed via flow cytometry (FCM) after 24 h of cultivation. In vitro migration of A549 and H1299 cells was determined by cell wound scratch assay after 0 h and 24 h culture. The caspase-3 and caspase-9 protein expression levels in A549 and H1299 cells were evaluated through western blot after 24 h of cultivation. Colony formation and EdU assays revealed that Z-ajoene could inhibit cell viability and cell proliferation in NSCLC cells. After 24 h culture, there was no significant difference in the proliferation rate of A549 and H1299 cells with different GE concentrations (P > 0.05). A remarkable proliferation rate difference emerged between A549 and H1299 cells with different GE concentrations after 48 and 72 hours of cultivation. The proliferation rate of A549 and H1299 cells in the experiment group was significantly lower than that in the control group. With an elevated level of GE concentration, the proliferation rate of A549 and H1299 cells decreased (P < 0.05) while the apoptotic rate increased continuously. GE could exert toxic effects on A549 and H1299 cells, inhibit cell proliferation, promote apoptosis, and attenuate cell migration. Meanwhile, it might induce apoptosis of A549 and H1299 cells through the caspase signal pathway, which is positively correlated with the mass action concentration and is expected to be a new drug for LC treatment.

An RNA-seq transcriptome analysis for investigating the anti-lung cancer activity of medicinal Cuscuta chinensis Lam plant.

Cuscuta chinensis Lam. is a traditional medicinal herb used to treat female sterility and male reproductive system disorders. However, the anti-lung cancer properties of Cuscuta chinensis Lam. and possible molecular mechanisms have yet to be explored. Thus, the study’s main purpose was to evaluate in vitro and in vivo anti-lung cancer properties of C. chinensis water extract (CLW) in human lung adenocarcinomas and the underlying molecular mechanism involved. Our results demonstrated that CLW caused a significant inhibition of cell viability and induced G1 cycle arrest in lung cancer cells. Furthermore, RNA-seq transcriptome analysis revealed 602 common genes with a significant expression in A549 and H1650 cells under CLW treatment. Functional enrichment analysis suggested that these common genes regulated by CLW mainly involve lung cancer cell proliferation, metastases and apoptosis processes. In addition, forty-six common genes (> 2-fold change) regulated by CLW in A549 and H1650 cells were selected for further validation. In vitro quantitative real-time PCR results confirmed that twelve genes were up-regulated, and four genes were down-regulated in A549 and H1650 cells. The in vivo experiment demonstrated CLW could significantly decrease tumour volume and tumour weight of mice compared with the control group. Moreover, in vivo quantitative real-time PCR results revealed that C11orf96, FGFBP1, FOSB and NPTX1 genes were up-regulated and EGR1, GBP4 and MAP2K6 genes were down-regulated in tumour tissues compared with the control group. These data strongly suggest that CLW could be developed as an efficacious drug for lung cancer treatment.

Dual-Drug Nanosystem: Etoposide Prodrug and Cisplatin Coloaded Nanostructured Lipid Carriers for Lung Cancer Therapy.

Cisplatin (CDDP) and etoposide (Etp) are recommended first-line therapy for lung cancer. Nanostructured lipid carriers (NLCs) are engineered to deliver drugs for lung cancer treatment. In the present study, NLCs were applied to coload an Etp prodrug (EtpP) and CDDP. The Etp prodrug was synthesized by linking the phenolic hydroxyl group of Etp with polyethylene glycol (PEG). EtpP and CDDP coencapsulated NLCs (EtpP-CDDP NLCs) were prepared using film ultrasound. Cytotoxicity of drugs and drug-containing NLCs was assessed by evaluating cell viability using MTT assays. In vivo antitumor efficiency of EtpP-CDDP NLCs was evaluated on lung cancer-bearing xenografts. EtpP-CDDP NLCs showed a uniformly spherical morphology with a size of 176.8±4.9 nm and -potential of -31.9±3.2 mV. Cellular uptake efficiency of EtpP-CDDP NLCs was 57.4%±3.9% on A549/DDP cells. EtpP-CDDP NLCs exhibited more sustained plasma retention, the highest drug distribution in tumors, and the highest tumor-inhibition rates in lung tumor-bearing mice. EtpP-CDDP NLCs improved tumor-cell uptake, cytotoxicity, and tumor-inhibition efficiency, and could be used as a promising drug-delivery system for lung cancer combination therapy.

Immune Checkpoint Inhibitors in Lung Cancer

With the fast increase in morbidity and mortality, lung cancer has become one of the greatest threats to physical health in some countries. Immune checkpoint inhibitors (ICIs) have a significant influence on the treatment landscape of lung cancer, including non-small cell lung cancer (NSCLC). This review highlights the most important ICIs used in lung cancer at present, anti-CTLA-4 and PD-1/L1. The application status, efficacy, shortcomings and prospect of each drug, including Ipilimumab (CTLA-4), Nivolumab, Pembrolizumab, and Durvalumab (PD-1/L1), are listed to show the drug indication in the current market. By comparing different drugs, the direction of ICI drug development can be more precise, which can have an important influence on choosing drugs for lung cancer treatment.

Hybrid Pharmacophore- and Structure-Based Virtual Screening Pipeline to Identify Novel EGFR Inhibitors That Suppress Non-Small Cell Lung Cancer Cell Growth.

Dysregulated epidermal growth factor receptor (EGFR) expression is frequently observed in non-small cell lung cancer (NSCLC) growth and metastasis. Despite recent successes in the development of tyrosine kinase inhibitors (TKIs), inevitable resistance to TKIs has led to urgent calls for novel EGFR inhibitors. Herein, we report a rational workflow used to identify novel EGFR-TKIs by combining hybrid ligand- and structure-based pharmacophore models. Three types of models were developed in this workflow, including 3D QSAR-, common feature-, and structure-based EGFR-TK domain-containing pharmacophores. A National Cancer Institute (NCI) compound dataset was adopted for multiple-stage pharmacophore-based virtual screening (PBVS) of various pharmacophore models. The six top-scoring compounds were identified through the PBVS pipeline coupled with molecular docking. Among these compounds, NSC609077 exerted a significant inhibitory effect on EGFR activity in gefitinib-resistant H1975 cells, as determined by an enzyme-linked immunosorbent assay (ELISA). Further investigations showed that NSC609077 inhibited the anchorage-dependent growth and migration of lung cancer cells. Furthermore, NSC609077 exerted a suppressive effect on the EGFR/PI3K/AKT pathway in H1975 cells. In conclusion, these findings suggest that hybrid virtual screening may accelerate the development of targeted drugs for lung cancer treatment.

GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma.

Simple SummaryLung adenocarcinoma is one of the leading causes of cancer-related deaths. Even though advanced anticancer drugs are available, prognosis of patients with lung cancer is dismal and there is an urgent need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. GPR87 is upregulated in various cancers, but its biological function has not yet been established in lung cancer. Here, we discovered that GPR87 is upregulated in lung adenocarcinoma and overexpressed GPR87 contributes to poor prognosis in patients with lung adenocarcinoma. We used GPR87-overexpressing and GPR87-silenced lung adonocarcinoma cell lines, along with in vivo studies, to demonstrate that overexpression of GPR87 promoted invasiveness and metastasis of lung adenocarcinoma cells. Our study identified the AKT-eNOS-NO signaling axis to be the mechanism by which GPR87 exerted its oncogenic function.Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2Tyr1007/1008 phosphorylation, and inhibits its downstream STAT3Tyr705 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.

Expression patterns and clinical significances of PBK in lung cancer: an analysis based on Oncomine database.

BackgroundBased on both biological and clinical perspectives, lung cancer is a diverse disease with varied histological subtypes. At present, molecular-targeted drugs have broad application prospects in lung cancer clinical therapy. Here, we explored the expression profile of PDZ-binding kinase (PBK) in lung cancer along with its prognostic potential.MethodsWe employed the Oncomine web resource to explore the differential expression of PBK in LC tissues. Additionally, the prognostic capacity of PBK in lung cancer was explored via the Kaplan-Meier Plotter web resource.ResultsOverall, 80 studies documented remarkable differences in the expression of PBK in tumor tissue and healthy control tissue. In all studies, 63 studies showed that PBK was upregulated and 17 studies demonstrated that PBK was downregulated. Of the 80 studies, 63 studies showed an increase in PBK expression in diverse kinds of tumor tissues including the following: bladder cancer, gastric cancer, brain and CNS cancer, cervical cancer, esophageal cancer, head and neck cancer, liver cancer, breast cancer, lung cancer, colorectal cancer, lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma and others. In addition, PBK expression was increased in 774 lung cancer tissues (P<0.05). Kaplan-Meier Plotter web resource analysis, revealed that PBK levels were negatively linked to the total survival period of individuals with lung cancer (P<0.05). Subgroup evaluations demonstrated that the prognostic significance of PBK was more obvious in individuals with lung adenocarcinoma. In lung cancer categorized by gender, level I-III differentiation, and stage 1 and stage 3 of clinical staging, the survival advantage of the PBK high-expression group was remarkably lower than that of the low-expression group lung cancer patients (P<0.05).ConclusionsPBK is an oncogene that is markedly upregulated in lung cancer tissues, and it is correlated with poor prognosis. PBK can be employed as a target in the design of new drugs for lung cancer treatment.

Formulation and Clinical Perspectives of Inhalation-Based Nanocarrier Delivery: A New Archetype in Lung Cancer Treatment

Despite tremendous research in targeted delivery and specific molecular inhibitors (gene delivery), cytotoxic drug delivery through inhalation has been seen as a core part in the treatment of the lung cancer. Inhalation delivery provides a high dose of the drug directly to the lungs without affecting other body organs, increasing the therapeutic ratio. This article reviews the research performed over the last several decades regarding inhalation delivery of various cancer therapeutics for the treatment of lung cancer. Nevertheless, pulmonary administration of nanocarrier-based cancer therapeutics for lung cancer therapy is still in its infancy and faces greater than expected challenges. This article focuses on the current inhalable nanocarrier-based drugs for lung cancer treatment.

Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway.

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview.

Simple SummaryAs lung cancer has the highest incidence rate compared to any other type of cancer, there have been extensive research studies aiming at finding a better treatment for curing this disease. One of the many approaches is by improving the delivery of anticancer drugs towards cancer cells using advanced technologies. In this review, we focused on docetaxel as one of the most commonly used drugs for lung cancer treatment and discussed the properties of the drug and the application of nanotechnology in delivering this drug to improve its efficacy and specificity while reducing its side effects. Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.

Design of a Novel Nucleus-Targeted NLS-KALA-SA Nanocarrier to Delivery Poorly Water-Soluble Anti-Tumor Drug for Lung Cancer Treatment.

In this study, we designed a novel nucleus-targeted nanocarrier (NLS-KALA-SA, NKSN) consisting of Kala peptide (KALA), nuclear localization signal (NLS) and stearic acid (SA) using Fmoc solid phase synthesis method. We chose Curcumin (CUR), Paclitaxel (PTX), Ginsenoside compound K(CK) as models of poorly water-soluble antitumor drugs, The drugs loaded NLS-KALA-SA nanoparticles (CUR/NKSN, PTX/NKSN, CK/NKSN) were obained by the dialysis method, their physicochemical properties were determined and antitumor activity were evaluated. The NLS-KALA-SA nanoparticles were spherical shaped with an average size of 76.4±7.6mm and a zeta potential of 43.7±5.8mV. The drug-loaded NLS-KALA-SA nanoparticles were above 86.1% and 17.1% in entrapment efficiency and drug loading capacity, and had sustained drug release behavior. Biodistribution and cellular uptake study exhibited that PTX/NKSN mainly distributed in tumor site of A549-bearing mice, and coumarin-6(C6) loaded NLS-KALA-SA nanoparticle (C6/NKSN) was predominantly accumulated in the nucleus of A549cells. Western blot analysis indicated that PTX/NKSN could more remarkably inhibit Bcl-2 expression and enhance the expression of Bax and Caspase-3 as compared to the controls in A549cells. Cell apoptosis and antitumor activity study showed that PXT/NKSN could more obviously induce apoptosis of A549cells compared with free PXT, the PTX/NKSN administration was more effective than free PTX for lung cancer treatment and displayed mild toxicity in A549-bearing mice. The results demonstrates that the NLS-KALA-SA nanoparticles system could enhance the antitumor effects of the encapsulated drug and reduce tissue toxicity due to its long circulating properties and tumor targeting, which might provide a promising strategy for lung cancer treatment.