Anti-lung Cancer Effect Research Articles

Elucidation of the anti-lung cancer mechanism of Juan-Liu-San-Jie prescription based on network pharmacology and experimental validation

Lung cancer is a malignancy characterized by high morbidity and mortality, with lung adenocarcinoma being the most prevalent subtype. Our preliminary studies have demonstrated that the Juan-Liu-San-Jie (JLSJ) prescription, a Traditional Chinese Medicine prescription, possesses anti-lung adenocarcinoma cancer properties. However, the molecular mechanism underlying the therapeutic effects of the JLSJ prescription for lung adenocarcinoma remains incompletely elucidated. To address the knowledge gap, the present study employed network pharmacology to identify potential therapeutic targets. Specifically, the study utilized TCMSP, TCMID, and related references, as well as ChemMapper, to identify and predict the main active components and potential targets. Additionally, differentially expressed genes associated with the disease were obtained from the microarray dataset GSE19804 and GSE118370. The protein-protein Interaction network and Target-pathway network were then constructed. We also conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and subsequently presented the top 20 enriched pathways. The results indicated that the anti-lung cancer effects of JLSJ prescription may be attributed to its ability to mediate apoptosis of tumor cells, potentially through the PI3K/Akt signaling pathway. Then, a series of in vitro and in vivo experiments were conducted to validate the molecular mechanism predicted by network pharmacology. The findings of the in vivo study suggested that the JLSJ prescription could inhibit the growth of xenograft tumors of lung adenocarcinoma with fewer adverse effects. Also, the in vitro experiments corroborated that the JLSJ prescription could induce apoptosis of A549 cells. Furthermore, the upregulation of pro-apoptosis-related proteins and mRNAs, coupled with the downregulation of anti-apoptotic-related proteins and mRNAs, was observed. In conclusion, inducing apoptosis by inhibiting the PI3K/Akt signaling pathway was one of the underlying mechanisms by which the JLSJ prescription exerted its anti-lung adenocarcinoma effect.

Ebracteolatain A Inhibits Lung Cancer Growth via p21 and p27 Mediated Cell-Cycle Arrest

Objective: Lung cancer is a refractory tumor with a poor five-year survival rate. Ebracteolatain A (EA), a key acetyl-phloroglucinol derived from the traditional Chinese herb Langdu, has been reported to have anti-tumor activity in human breast cancer. However, the therapeutic efficacy and underlying mechanism of lung cancer remain to be elucidated. In the present study, we intended to evaluate whether EA exhibits anti-lung cancer activity and elucidate the underlying mechanisms. Methods: ATPlite and clonogenic survival assays were used to assess the inhibiting effect of EA on two lung cancer cell lines in vitro. FACS was conducted to determine the cell-cycle profiling of lung cancer cells upon treatment with EA. Western blot was performed to detect the level of related proteins in EA-treated lung cancer cells. RNA silencing and other experiments were used to identify the molecular mechanism of EA-triggered cell-cycle arrest. Furthermore, a xenograft tumor model was constructed to evaluate the therapeutic effect and potential mechanism of EA in vivo in mice. Results: EA significantly inhibited the growth of lung cancer cells both in vitro and in vivo. Mechanistically, EA-induced G1 phase cell-cycle arrest is mediated by the accumulation of p21 and p27. Conclusion: Our findings revealed the anti-lung cancer effect of EA and the mechanisms, providing a solid scientific basis for EA as an attractive choice for lung cancer therapy.

Co-delivery of berberine and magnolol targeted liposomes for synergistic anti-lung cancer

Lung cancer is the leading cause of both new cancer cases and deaths. Both Berberine (BBR)and Magnolol (MAG) have specific anti-lung cancer effects. However, the adverse properties of direct administration of BBR and MAG largely limited the anti-cancer effects, such as short circulation time and poor selectivity. In this work, the optimal molar ratio of BBR to MAG (2:1) was chosen based on the synergistic anti-lung cancer effect. The chondroitin sulfate (CS) modified liposomes (CS-Lip-MB) were developed to co-deliver BBR and MAG by the film dispersion combined with the pH gradient method, which could specifically bind to the CD44 receptor highly expressed A549 cells, thus improving the tumor targeting and synergistic anti-cancer effect. The optimum composition of the formulation (weight ratio) hydrogenated soy phospholipid (HSPC): cholesterol: stearylamine:MAG:BBR was 18:5:0.69:1:1 with the CS concentration of 3 mg·mL−1. CS-Lip-MB showed extended drug release performances, and improved the uptake by A549 cells, thus enhancing the toxicity and migration-blocking impact on tumor cells, and promoting cell apoptosis. The apoptosis mechanism is related to the regulation of the expressions of Bcl-2, Bax and Caspase-3. Meanwhile, the results of in vivo biodistribution and pharmacokinetics indicated that CS-Lip-MB could improve the blood stability, prolong the circulation time, and increase in vivo targeting of free drugs. CS-Lip-MB significantly inhibited tumor growth and reduced toxic side effects in A549-bearing nude mice with the highest tumor inhibition rate of 81.48%. In summary, CS-Lip-MB liposomes exhibited great potential for synergistic therapy of lung cancer with improved blood stability, excellent targeting ability and superior in vivo anti-lung cancer effect.

Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice.

Sulfasalazine (SAS) is a repurposed antitumor drug which inhibits the proliferation and survival of cancer cells by inhibiting the xCT cellular antioxidant system. Recent clinical studies have shown that, due to poor bioavailability, the antitumor effects of SAS monotherapy are minimal. Therefore, we hypothesized that DSF, another repurposed drug that has demonstrated anticancer effects, or its complex with copper (DSF-copper, DSF-Cu) could potentiate the antilung cancer effects of SAS. Exposure of non-small cell lung cancer cells to therapeutically achievable concentrations of SAS-induced low-to-moderate cytotoxic effects (20-40% reduction in cell viability) and, unexpectedly, induced the antioxidant protein NRF2 and its downstream effectors xCT and ALDH1A1. However, combinations of SAS and DSF-Cu, but not SAS and DSF, induced a significantly higher cytotoxic effect (64-88% reduction in cell viability), apoptosis and generation of mitochondrial reactive oxygen species as compared with SAS or DSF-Cu alone. Moreover, DSF-Cu abrogated SAS-induced NRF2, xCT and ALDH1A1 expression. In a mouse model of lung tumor, SAS + DSF-Cu showed a higher efficacy than the individual drugs in reducing the number and size of tumors as well as the incidence and multiplicity of lung adenocarcinoma. Taken together, our findings indicate that the observed antilung cancer effects of SAS plus DSF-Cu are mediated, at least in part, via impairment of reactive oxygen species defense and -enhancement of oxidative stress and provide evidence for the preventive/therapeutic potential of this combinatorial approach against lung cancer.

Formulation of a novel anti-lung cancer drug: Vanadium nanoparticles containing Salvia officinalis

In this study, vanadium nanoparticles were green synthesized using the aqueous extract of Salvia officinalis. Different techniques such as FE-SEM, XRD, FT-IR, and EDS analysis were used to characterize VNPs@Salvia officinalis. A 25.6 nm was obtained for the crystal size of the vanadium nanoparticles using XRD analysis. The FE-SEM images show a spherical morphology for VNPs@Salvia officinalis with the range size of 11.28 to 40.74 for the synthetic nanoparticles. In the antioxidant test, the IC50 of VNPs@Salvia officinalis and BHT against DPPH free radicals were 300 and 265 µg/mL, respectively. For anticancer activity evaluation the treated cells with VNPs@Salvia officinalis were assessed by MTT assay for 48 h about the cytotoxicity and anti-lung cancer properties on normal (HUVEC) and lung cancer cell lines i.e., EBC-1, LK-2, LU65, LU99, STC 1 and RERF-LC-MA. The IC50 of VNPs@Salvia officinalis were 213, 210, 297, 204, 160, and 125 µg/mL against EBC-1, LK-2, LU65, LU99, STC 1 and RERF-LC-MA cell lines, respectively. The viability of malignant lung cell lines reduced dose-dependently in the presence of VNPs@Salvia officinalis. It appears that the anti-lung cancer effect of VNPs@Salvia officinalis is due to their antioxidant effects.

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease.

Lung cancer is the malignancy with the highest morbidity and mortality. Additionally, pulmonary inflammatory diseases, such as pneumonia, acute lung injury, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF), also have high mortality rates and can promote the development and progression of lung cancer. Unfortunately, available treatments for them are limited, so it is critical to search for effective drugs and treatment strategies to protect the lungs. Ginsenosides, the main active components of ginseng, have been shown to have anti-cancer and anti-inflammatory activities. In this paper, we focus on the beneficial effects of ginsenosides on lung diseases and their molecular mechanisms. Firstly, the molecular mechanism of ginsenosides against lung cancer was summarized in detail, mainly from the points of view of proliferation, apoptosis, autophagy, angiogenesis, metastasis, drug resistance and immunity. In in vivo and in vitro lung cancer models, ginsenosides Rg3, Rh2 and CK were reported to have strong anti-lung cancer effects. Then, in the models of pneumonia and acute lung injury, the protective effect of Rb1 was particularly remarkable, followed by Rg3 and Rg1, and its molecular mechanism was mainly associated with targeting NF-κB, Nrf2, MAPK and PI3K/Akt pathways to alleviate inflammation, oxidative stress and apoptosis. Additionally, ginsenosides may also have a potential health-promoting effect in the improvement of COPD, asthma and PF. Furthermore, to overcome the low bioavailability of CK and Rh2, the development of nanoparticles, micelles, liposomes and other nanomedicine delivery systems can significantly improve the efficacy of targeted lung cancer treatment. To conclude, ginsenosides can be used as both anti-lung cancer and lung protective agents or adjuvants and have great potential for future clinical applications.

Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Tumor-associated macrophages (TAMs) participate in tumorigenesis, growth, invasion as well as metastasis by facilitating an immunosuppressive tumor microenvironment. Reversing the pro-tumoral M2 phenotype of TAMs has become a hot spot in advancing cancer immunotherapy. In the current study, the content of Moringa oleifera leaf polysaccharides (MOLP) was determined and characterized, along with the anti-cancer mechanism of MOLP studied in a Lewis lung cancer (LLC) tumor-bearing mouse model and bone marrow-derived macrophages. The monosaccharide composition and gel permeation chromatography analyses show that MOLP are mainly composed of galactose, glucose, and arabinose, with approximately 17.35 kDa average molecular weight (Mw). In vivo studies demonstrate that MOLP convert TAMs from the immunosuppressive M2 phenotype to the antitumor M1 phenotype, thus inducing CXCL9 and CXCL10 expression and increasing T-cell infiltration in the tumor. Furthermore, macrophage depletion and T cell suppression demonstrated that the tumor suppressive effect of MOLP was reliant on reprogramming macrophage polarization and T cell infiltration. In vitro studies revealed that MOLP could induce the phenotypic switch from M2 macrophages to M1 by targeting TLR4. The current study highlights that MOLP are promising anticancer plant-derived polysaccharides with potential in modulating the immune microenvironment and have a bright application prospect in the immunotherapy of lung cancer.

Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation.

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.

Co-Fermentation of Marsdenia tenacissima with Ganoderma lucidum and Anti-Lung Cancer Effect of the Fermentation Products.

Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), as a traditional Chinese and Dai herbal medicine, has anti-inflammatory, antibacterial, and antitumor properties. However, most of its main active substances are aglycones, such as tenacigenin A and tenacigenin B. As the bioavailability of MT is low and its medicinal active components are challenging to synthesize, it is primarily studied by biotransformation. This study aims to produce biotransformation products rich in pungent saponins by using MT as a fermentation medium for Ganoderma lucidum (G. lucidum). Through the preliminary screening of three medicinal fungi, it was found that G. lucidum and Ophiocordyceps sinensis (O. sinensis) can generally grow in the medium for MT; hence, the efficacy of the fermentation of the two types of fungi was screened using a mouse model of lung cancer. Finally, the co-fermentation of G. lucidum and MT was selected for further investigation. Non-target metabolomics analysis was performed on the products of MT with G. lucidum co-fermentation. We identified 12 specific saponins of MT from the fermentation products, and obtained a monomeric compound, tenacigenin A, from fermentation products. Most of the tenacigenin showed a significant upward trend, through tenacigenin A and tenacigenin B levels. The results showed that the efficacy of MT improved after fermentation by G. lucidum. Furthermore, the biotransformation of C21 steroidal glycosides in MT was the central reaction in this fermentation process. In summary, this study established a systematic and comprehensive co-fermentation system and pharmacodynamic evaluation method for MT, which not only enhanced the full utilization of effective active substances in MT but also provided a methodological reference for the development of other ethnic drugs.

Green synthesis of Ag/Fe3O4 nanoparticles using Mentha longifolia flower extract: evaluation of its antioxidant and anti-lung cancer effects

Herein, a bio-inspired synthetic method for Ag NP adorned biofunctionalized magnetic nanocomposite has been demonstrated. In the procedure, Mentha longifolia flower extract was employed as a template for the green reduction of immobilized Ag ions to corresponding NPs and subsequent stabilization. The phytochemical modification also facilitated the Fe3O4 NPs to protect from self-aggregation. The as-synthesized Ag/Fe3O4 nanocomposite material was characterized by SEM, TEM, EDX, elemental mapping, VSM, XRD and ICP-OES methods. Towards the biological application, the material was first explored in the anti-oxidant study following DPPH assay and it exhibited a significant radical scavenging capacity. The application of Ag/Fe3O4 nanocomposite was further progressed in the anticancer study against standard human lung cancer cell lines (A549 and H358). Cytotoxicity of the material against the cell lines were determined in terms of % cell viability following MTT method and was found to decrease with increase in the material load.

Isoginkgetin inhibits lung cancer cell progression through miR-27a-5p/APEX1 axis

Purpose: To determine the influence of isoginkgetin on the progression of pulmonary carcinogenesis.
 Methods: A549 cells exposed to isoginkgetin were transfected with miR-27a-5p mimetic and suppressor, as well as short hairpin RNA against apurinic/apyrimidinic endo-deoxyribonuclease 1 (sh-APEX1) for 24 h. Then, the proliferative, migration and invasive potential of A549 cells were determined using CCK-8, wound healing and Transwell assays, respectively. The association between miR-27a-5p and APEX1 was determined by dual-luciferase reporter assay.
 Results: Isoginkgetin significantly suppressed A549 cell proliferative, migration and invasive activities (p < 0.05). Moreover, isoginkgetin significantly increased miR-27a-5p expression. Furthermore, miR-27a-5p suppressor annulled the influence of isoginkgetin on lung cancer progression. More importantly, the inhibitor directly targeted APEX1, and negatively modulated APEX1 expression (p < 0.05). However, APEX1 knockdown annulled the enhancing effect of miR-27a-5p inhibitor on A549 cell viability, migration and invasion (p < 0.05).
 Conclusion: Isoginkgetin exerts an anti-lung cancer effect via miR-27a-5p/APEX1 axis. Thus, it is a potential therapy for the management of lung cancer; however, clinical studies are required to validate these findings of this study.

Arsenic Trioxide Restrains Lung Cancer Growth and Metastasis by Blocking the Calcineurin-NFAT Pathway by Upregulating DSCR1.

Anti-angiogenesis therapy mostly aimed at targeting vascular endothelial growth factor (VEGF) and its receptors have been widely applied to lung cancer. However, the improvement in the patient's overall survival remains dissatisfying. Previously, we demonstrated that arsenic trioxide (As2O3) exerts an anti-lung cancer effect through anti-angiogenesis, but the details of the mechanism in play remain unclear. Herein, we focused on the calcineurin-NFAT pathway, downstream of VEGF, and its endogenous inhibitor DSCR1. To demonstrate the mechanism of As2O3 restraining lung cancer growth and metastasis by blocking the calcineurin-NFAT pathway by upregulating DSCR1. We constructed xenografts and metastasis models based on wild-type (WT) and DSCR1 knockout (DSCR1-/-) mice, and carried out qPCR, Western blot, immunohistochemistry, in vivo imaging and calculated microvessel density to evaluate the effects of As2O3 on angiogenesis, tumor growth, metastasis, and the protein expression levels of DSCR1 and calcineurin-NFAT pathway-related molecules. As2O3 inhibited tumor growth and metastasis, reduced microvessel formation, and induced vascular lumen malformation in WT mice. At the protein level, As2O3 upregulated DSCR1, downregulated NFAT2 and its downstream molecules, but had no effect on calcineurin A. However, in DSCR1-/- mice, the above-mentioned effects of As2O3 were abolished. As2O3 can suppress lung cancer growth and metastasis through anti-angiogenesis effects by blocking the calcineurin-NFAT pathway by upregulating DSCR1. The results shed light on the antitumor mechanism of As2O3 and are a step forward in the identification of As2O3 as a new drug in the treatment of lung cancer.

Research Progress of Anti-lung Cancer Effect of Quercetin in Vitro

Research Progress of Anti-lung Cancer Effect of Quercetin in Vitro

EEF‐2K knockdown synergizes with STS treatment to inhibit cell proliferation, migration, and invasion via the TG2/ERK pathway in A549 cells

Emerging research has suggested the anticancer potential of tanshinone IIA, the bioactive ingredient isolated from the traditional Chinese herb Salvia miltiorrhiza. However, the molecular mechanism of sodium tanshinone IIA sulfonate (STS) antilung cancer effect is not very clear. In this study, our purpose is to investigate the roles of STS and elongation factor-2 kinase (eEF-2K) in regulating the proliferation, migration, and invasion of A549 cells and explore the implicated pathways. We found that STS suppressed A549 cell survival and proliferation in a time- and xdose-dependent manner. Knockdown of eEF-2K and treatment with STS synergistically exerted antiproliferative, -migratory, and -invasive effects on A549 cells. These effects were caused by attenuation of the extracellular signal-regulated kinase(ERK) pathway via inhibition of tissue transglutaminase (TG2). In summary, the inhibition of eEF-2K synergizes with STS treatment, exerting anticancer effects on lung adenocarcinoma cells through the TG2/ERK signaling pathway, which provides a potential therapeutic target for treating lung adenocarcinoma.

Optimizing component formula suppresses lung cancer by blocking DTL-mediated PDCD4 ubiquitination to regulate the MAPK/JNK pathway

Ethnopharmacological relevanceSalvia miltiorrhiza Bunge and Panax ginseng C. A. Meyer have special curative effect on cancer treatment. The optimizing component formula (OCF) extracted from those two herbs was in line with the anti-lung cancer treatment principle of activating blood and supplementing ‘Qi’. However, the study on the mechanism of component formula has always been an insurmountable challenge. Nowadays, the application of network pharmacology and artificial intelligence (AI) in the field of TCM provides new ideas for the study of new targets and mechanisms of TCM, which promotes the modernization of TCM. Aim of the studyThis study aims to further explore the anti-lung cancer mechanism of OCF by using an integrated strategy of network pharmacology and AI technology. Materials and methodsBioinformatic analysis was used to analyze the expression levels, prognosis and survival of DTL and PDCD4 in cancer patients. The binding strength of OCF and DTL was simulated by molecular docking, and the affinity between them was detected by Bio-layer interferometry. Network pharmacology was used to predict the active components, potential targets and pathways of OCF. The association between key targets and their corresponding components and DTL was analyzed by Ingenuity Pathway Analysis (IPA). MTT assay, colony formation assay, wound-healing assay and transwell assay were used to verify the inhibitory effects of OCF on lung cancer cells in vitro. qRT-PCR and Western blot assay were used to detect the effects of OCF on mRNA and protein expression of DTL, PDCD4 and key genes in MAPK/JNK pathways. ResultsBioinformatics analysis showed that DTL was significantly up-regulated in lung cancer, which was associated with high malignancy rate, high metastasis rate and poor prognosis of primary tumor. PDCD4 was down-regulated in lung cancer, and associated with high metastasis rate and poor prognosis. The good affinity between OCF and DTL was predicted and verified by molecular docking and Bio-layer interferometry. Based on the network pharmacological databases, 40 active components and 220 corresponding targets of OCF were screened out. KEGG analysis showed that OCF component targets were mainly enriched in MAPK signaling pathway. IPA results showed the interrelationship between DTL, PDCD4, MAPK pathway genes and their corresponding OCF components. In addition, in vitro experiments demonstrated anti-lung cancer activity of OCF, as validated, via impairing cell viability and cell proliferation, as well as inhibiting migration and invasion abilities in lung cancer cells. qRT-PCR showed that OCF down-regulated the mRNA expression of DTL, MAP4K1, JNK, c-Jun and c-Myc, and up-regulated the mRNA expression of PDCD4 and P53 genes in A549 lung cancer cells. Western blot suggested that OCF suppressed the protein level of DTL and blocked the ubiquitination of PDCD4 in A549 lung cancer cells, and down-regulated the protein levels of MAP4K1, p-JNK and p-c-Jun while up-regulated the proteins expression level of P53. ConclusionsOCF might elicit an anti-lung cancer effect by blocking DTL-mediated PDCD4 ubiquitination and suppression of the MAPK/JNK pathway. Meanwhile, our work revealed that network pharmacology and AI technology strategy are cogent means of studying the active components and mechanism of TCM.

To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology.

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology.The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language.In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The “component-target” network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer.Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.

Anti-lung cancer effect of paclitaxel solid lipid nanoparticles delivery system with curcumin as co-loading partner in vitro and in vivo

The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (–30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-κB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.

Identification of molecular mechanism of the anti-lung cancer effect of Jin Ning Fang using network pharmacology and its experimental verification

Jin Ning Fang (JNF), a classic Chinese medicine formula, is widely used to treat lung cancer. However, its molecular mechanism remains unclear. Thus, we aimed to explore the pharmacological mechanisms of JNF against lung cancer. JNF targets and lung cancer-related genes were derived from public databases. Key compounds, potential therapeutic targets, and pathways were determined via bioinformatics analyses. Further, molecular docking, in vitro experiments, and real-time PCR were performed to verify the findings. A total of 27 active compounds and 25 genes were selected. Pharmacological network revealed that quercetin, calcium carbonate, and beta-sitosterol might be candidate agents; ESR1, AR, AKT1, FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ANPEP could be potential drug targets. These genes were involved in apoptosis pathway. Docking analysis showed that beta-sitosterol combined well with AKT1, AR, and ESR1. In vitro experiments confirmed that JNF could inhibit proliferation and promote apoptosis of A549 cells. JNF treatment inhibited the level of FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ESR1, while increased the level of AR and ANPEP. This study illuminated that JNF exerts anti-lung cancer effects through regulating multiple targets and pathways, and the identified genes may be used as potential therapeutic targets for lung cancer.

Oak gum mediated green synthesis of silver nanoparticles under ultrasonic conditions: Characterization and evaluation of its antioxidant and anti-lung cancer effects

Herein, we represent the bio-synthesis of silver nanoparticles (Ag NPs) employing Oak gum as the green template, an efficient natural and non-toxic reductant and stabilizer based on its phytochemicals by using ultrasonic irradiation. The characterization of as-synthesized Ag NPs was performed through Fourier transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), elemental mapping, UV–Vis and X-ray diffraction (XRD). After the characterization, the synthesized Ag NPs/O. Gum was engaged in biological assays like study of anti-oxidant properties by DPPH mediated free radical scavenging test using MeOH and BHT as reference molecules. Thereafter, on having a significant IC 50 value in radical scavenging assay, we extended the bio-application of the desired nanocomposite in anticancer study of A549, Calu6 and H358 human lung cell lines in-vitro through MTT assay. They had very low cell viability and high anti-human lung cancer activities dose-dependently against the cell lines without any cytotoxicity on the normal cell line (MRC-5). The IC 50 of Ag NPs/O. Gum was found 161.25, 289.26 and 235.29 µg/mL against A549, Calu6 and H358 cell lines, respectively. Maybe significant anti-human lung cancer potentials of Ag NPs/O. Gum against common lung cancer cell lines are related to their antioxidant activities. So, these results suggest that synthesized Ag NPs/O. Gum as a chemotherapeutic nanomaterial have a suitable anticancer activity against lung cell lines.

Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway

Lung cancer poses a serious threat to human health. Although targeted therapies have led to breakthroughs in the treatment of lung cancer, drug resistance and side effects limit their clinical applications. Xihuang pill (XHW), a classical anti-cancer traditional Chinese medicine formula, has been clinically proven to be an effective complementary therapy in the treatment of various of cancers. However, the underlying mechanism for its use in combination with anti-cancer drugs remains unclear. Here, we explored the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung cancer (LLC). We used gut microbiota and transcriptomics to elucidate the regulatory properties of XHW in improving anti-lung cancer effect of anlotinib. The results showed that combination treatment of XHW with Anlotinib significantly inhibited tumor growth in LLC-bearing mice. We found that XHW played a key role in the regulation of gut microbiota using 16 s rRNA sequencing analysis. Specifically, XHW increased the proportion of the beneficial bacteria Bacteroides and g_norank_f_Muribaculaceae. Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients.