Digestive System Malignancies Research Articles

Insight of pancreatic cancer: recommendations for improving its therapeutic efficacy in the next decade

Pancreatic cancer is one of the most malignant digestive system tumors. The effectiveness of pancreatic cancer treatment is still dismal, and the 5-year survival rate is only about 10%. Further improving the diagnosis and treatment of pancreatic cancer is the top priority of oncology research and clinical practice. Based on the existing clinical and scientific research experience, the review provides insight into the hotspots and future directions for pancreatic cancer, which focuses on early detection, early diagnosis, molecular typing and precise treatment, new drug development and regimen combination, immunotherapy, database development, model establishment, surgical technology and strategy change, as well as innovation of traditional Chinese medicine and breakthrough of treatment concept.

Value of MSCT plus MRI in the Detection of Colon Cancer.

Colon cancer is a common digestive system malignancy with nonspecific early symptoms, which necessitates better early detection methods. The present study was conducted to assess the accuracy and clinical value of multislice spiral CT (MSCT) plus magnetic resonance imaging (MRI) for colon cancer. Between January 2019 and July 2020, 100 patients with pathologically confirmed colon cancer treated in Wuxi People's Hospital were assessed for eligibility and recruited. All eligible patients received MRI and MSCT without any treatment prior to scanning. The accuracy of preoperative diagnosis and staging of colon cancer by MRI, MSCT, and MRI plus MSCT were analyzed using postoperative pathological results as the gold standard, and consistency analysis was performed. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was obtained to analyze the preoperative diagnostic value. The accuracy of MRI, MSCT, and MRI plus MSCT was 98.00%, 96.00%, and 100% with good consistency (Kappa = 0.732, 0.703, and 0.756). The AUC of MRI, MSCT, and MRI plus MSCT was 0.889, 0.861, and 0.903, respectively. The preoperative diagnostic accuracy of MRI for colon cancer at T1, T2, T3, and T4 stages was 76.92%, 82.61%, 73.47%, and 86.67%, respectively, those of MSCT was 53.85%, 69.57%, 63.27%, and 40.00%, respectively, and those of MRI plus MSCT was 100.00%, 95.65%, 95.92%, and 86.67%, respectively. Consistency analysis yielded good consistency for the diagnosis of the T-staging of colon cancer (Kappa = 0.754, 0.731, 0.776). MSCT plus MRI yielded higher accuracy, specificity, and sensitivity in the detection of colon cancer versus the standalone MRI or MSCT, which demonstrated great potential in the early detection of colon cancer with a high clinical value.

LncRNA MIR600HG induces the proliferation and invasion of colorectal cancer cells via regulating miR-144-3p/KIF3A

Colorectal cancer (CRC) is a common digestive system malignancy characterized by the high morbidity and mortality rates. Due to the limited therapeutic options, the majority of CRC patients do not receive timely treatment, which has thus increased the risk of tumor recurrence. Long noncoding RNAs (lncRNAs), as the essential regulators, are involved in numerous pivotal physiological and pathological processes in CRC. By qRT-PCR, it could be discovered in this study that MIR600HG expression obviously increased in CRC tissues and cell lines compared with the normal group. Moreover, the high expression of MIR600HG was correlated with tumor size, tumor volume and TNM stage. Overexpression of MIR600HG affected the expression of downstream molecules, such as miR-144-3p and KIF3A, providing the possible mechanisms of MIR600HG in the development and progression of CRC.

LncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells.

Gastric cancer (GC) is one of the most common malignancies in digestive system. Accumulating evidence reveals the critical role of long noncoding RNAs (lncRNAs) in GC development. The study aimed to explore the functions and mechanism of lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) in GC. Reverse transcription-quantitative polymerase chain reaction analyses and subcellular fractionation assays showed that ACTA2-AS1 was lowly expressed in GC cells and was mainly distributed in the cytoplasm. Overexpressed ACTA2-AS1 inhibited GC cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition process, as suggested by cell counting kit-8 assays, colony formation assays, wound healing assays, Transwell assays and Western blot analyses. Mechanistically, ACTA2-AS1 served as a competing endogenous RNA (ceRNA) to bind with miR-378a-3p and thereby, antagonized the inhibitory effect of miR-378a-3p on the expression of messenger RNA phosphatidylinositol specific phospholipase C X domain containing 2 (PLCXD2). The binding capacity between miR-378a-3p and ACTA2-AS1 (or PLCXD2) was detected by RNA pulldown assays, luciferase reporter assays and RNA immunoprecipitation assays. Moreover, PLCXD2 knockdown rescued the inhibitory effect of ACTA2-AS1 overexpression on malignant behaviors of GC cells. Overall, ACTA2-AS1 inhibits malignant phenotypes of GC cells by acting as a ceRNA to target miR-378a-3p/PLCXD2 axis.

Ten-year data analysis of digestive system malignancies in Babol, North of Iran: 2008-2017.

Background:Unlike some regions of the world where digestive system cancers are not considered as important health problems, these neoplasms are among the most common malignancies in the northern region of Iran.Methods:This observational analytical study was carried out based on data collected by the Cancer Registration Center affiliated to the Vice Chancellery for Health of Babol University of Medical Sciences, North of Iran, during 2008-2017. Crude incidence rate (CR), and age-standardized incidence rate (ASR) have been calculated for different GI cancers, based on the primary involved site; and have been compared in different years, patients' age, gender and place of residence.Results:Totally, 4332 records were related to digestive system cancers. Mean age of patients was 63.48±14.73 years; men (2743; 63.3%) were more affected than women (1589; 36.7%) (p<0.001). The most incident malignancies of digestive system were from stomach, colorectal and esophagus in men; and colorectal, stomach and esophagus in women, respectively. These three cancers accounted for 3725 (85.98%) of total GI malignancies. The mean age of patients in various types of GI cancers was statistically different (p<0.001). Age- standardized incidence rate showed different values in different years; from 521.40 (95% CI: 462.79-580.00) in year 2016 to 1834.33 (95% CI: 1637.36-2031.29) in year 2008.Conclusion:Gastric, esophageal and colorectal cancers were the most prevalent digestive system malignancies in Babol, North of Iran, and accounted for about 86% of all GI tract cancers. A considerable variation has been found in incident gastrointestinal cancers in different years.

Periostin: a predictable molecule to prognosis and chemotherapy responses of gastrointestinal and hepato-biliary-pancreatic malignant tumors?

With the continuous development of medical science and technology, the medical community's understanding of the disease is constantly updated, just as strategies for treating malignant tumors are constantly updated. New diagnoses, follow-up indicators, and treatment plan formulations need more evidence to be supported. To date, radical surgical resection is still the preferred treatment for advanced digestive system malignancies, and combination therapy including chemotherapy and targeted therapy before or after surgery is aimed at improving the prognosis and quality of life of patients. However, if tumor recurrence, metastasis, chemotherapy, and drug resistance to targeted agents after surgery prevent the achievement of the desired therapeutic effect, and if neoadjuvant chemotherapy and targeted therapy cannot reduce the staging of the tumor, surgery cannot be performed. These are huge problems that we face now and will continue to face for some time. Relevant scientific data and evidence have been produced to explain unsatisfactory efficacy, such as epithelial-mesenchymal transformation, the tumor microenvironment, extracellular matrix proteins, cancer-related fibroblasts, and other factors that may be related to tumor progression and poor therapeutic effects. An extracellular matrix protein, periostin (POSTN), influences the above factors and has received multidisciplinary attention. In this paper, periostin and digestive system-related tumors are reviewed, and the production, mechanism of action, drug resistance correlation analysis, and coping strategies of periostin are summarized to further understand its characteristics. This work provides evidence for potential therapeutic targets for digestive system tumors in the future.

Ten directions for improving clinical therapeutic effect of pancreatic cancer in the future

Pancreatic cancer is one of the most malignant digestive system tumors. In the recent decade, the effect of diagnosis and treatment of pancreatic cancer has improved due to the renewal of treatment concept and the popularization of effective treatment. However, the overall efficacy of pancreatic cancer is still dismal and the 5-year survival rate is only about 10%. Further improving the diagnosis and treatment of pancreatic cancer is the top priority of oncology research and clinical practice. Based on past clinical and scientific research experience, the authors have proposed ten hot spots and future directions for a reference, which focusing on early prevention, early diagnosis, and early treatment of pancreatic cancer, molecular typing and precise treatment, new drug development and regimen combination, surgical technology and strategy change, model establishment and database development, as well as innovation of traditional Chinese medicine and breakthrough of treatment concept. A breakthrough in the diagnosis and treatment of pancreatic cancer in the next ten years is raising hope, when doctors can truly prevent and control pancreatic cancer.

Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer.

Worldwide, cancer is the second leading cause of mortality after cardiovascular diseases. Among the numerous malignant tumors in human, digestive system cancers are the primary cause of morbidity and mortality. Acetylation and deacetylation are crucially involved in cancer occurrence and development; in addition, the deacetylation process is regulated by histone deacetylases (HDACs). Among the 18 human HDACs that have been reported, HDAC6 has been widely studied. There is upregulated HDAC6 expression in numerous types of tumor tissues and is closely associated with clinicopathological characteristics. Moreover, several HDAC6 inhibitors have been identified; furthermore, there has been extensive research on their ability to inhibit the growth of many tumors. This review summarizes the roles of HDAC6 in different primary digestive system malignancies.

Incidence and characteristics of death from peptic ulcer among cancer patients in the United States

Most cancer patients die of non-cancer causes, and peptic ulcer is one cause that deserves attention. To characterize the incidence and risk factors of death from peptic ulcer among cancer patients, we extracted the data of cancer patients registered in the Surveillance Epidemiology and End Results (SEER) program from 1975 to 2016. Out of the 8,471,051 patients extracted from SEER, 4,698 died from peptic ulcer, with a mortality rate of 9.08/100,000 person-years. Meanwhile, the mortality rate in the general population was 5.09/100,000 person-years, giving a standardized mortality ratio (SMR) of 1.78 (95% confidence interval, 1.73–1.84). Patients who are female, of other race, unmarried, and with distant tumor stage have greater SMRs. A higher SMR was associated with a younger age at diagnosis. Among those aged < 40 years at diagnosis, the plurality of fatal peptic ulcers occurred in patients with leukemia and lymphoma, while in patients aged > 40 years, the majority occurred in those with prostate, breast, colorectum, and lung cancer. Patients with upper digestive system malignancies had the highest SMRs and hazard ratios (HRs), which could be ascribed to radiotherapy-induced damage to the gastroduodenum. The risk declined rapidly one year after diagnosis. However, the SMRs in the upper digestive system cancer survivors increased significantly over ten years after diagnosis. Upper digestive system cancers adjacent to the gastroduodenum were associated with higher SMRs and HRs compared with other types of cancer, possibly contributing partially to the damage caused by radiotherapy on the radiosensitive gastroduodenum.

Long noncoding RNA SOX2OT promotes pancreatic cancer cell migration and invasion through destabilizing FUS protein via ubiquitination

Pancreatic cancer is a highly aggressive and lethal digestive system malignancy. Our previous studies revealed the correlation of high levels of lncRNA SOX2OT expression with patients’ poor survival outcomes, the promoting role of SOX2OT in proliferation and cycle progression of pancreatic cancer cells, and the in vivo binding of SOX2OT to RNA binding protein FUS, which destabilized the protein expression of FUS. However, the mechanism of SOX2OT binding and inhibiting FUS protein stability remains unclear. In this study, we performed RNA pull-down, cycloheximide-chase, and ubiquitination assays to determine the effect of SOX2OT on FUS ubiquitination, and explored the specific regulatory mechanism of SOX2OT–FUS axis in pancreatic cancer cell migration, invasion, in vivo tumor growth, and metastasis through RNA sequencing. We found that SOX2OT binds to FUS through its 5′ and 3′ regions, resulting in FUS ubiquitination and degradation. The SOX2OT–FUS regulatory axis promotes migration, invasion, tumor growth, and metastasis ability of pancreatic cancer cells. The in-depth elaboration of the SOX2OT–FUS regulatory axis in pancreatic cancer may clarify the mechanism of action of SOX2OT and provide new ideas for pancreatic cancer treatment.

Real-world data on camrelizumab in digestive system cancers: a retrospective observational study

Objective: To explore the clinical efficacy and safety of camrelizumab in the treatment of digestive system malignancies in the real world. Methods: A retrospective study was designed. A total of 34 patients with advanced gastrointestinal cancer who received camrelizumab treatment in the xx hospital from July 2019 to May 2020 were included. The follow-up endpoint was set for October 30, 2020. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoint measures included progression-free survival (PFS), and overall survival (OS). Cox regression was used for the analysis of factors associated with PFS. Results: As the best response, only 5 patients achieved a partial response and 10 patients had disease progression, with an ORR of 14.31%. Compared with gastric cancer, the ORR of esophageal cancer (3.0% vs 0.0%) (P&lt;0.05). The PFS was 4.5 months (2-10 months). OS ranged from 4 to 11 months, and median OS has not been reached. Multivariate Cox regression analysis showed that gastric cancer (HR=1.695, 95% CI:11.216–2.435, P&lt;0.05) was associated with still shorter PFS, and camrelizumab combined with other drugs (HR=0.512, 95% CI: 0.095–0.737, P&lt;0.01) was associated with PFS in patients. The most common AEs were anemia (41.2%, 14/34) in all grades 1 to 2. Grade 3 AEs occurred in 3 patients (2.9%), including 1 case of immune pneumonitis, 1 case of hemangioma, and 1 case of transaminase increased. Other adverse events included diarrhea, nausea, neutropenia, thrombocytopenia, reactive cutaneous capillary proliferation (RCCEP), fatigue, and hypothyroidism, all of which did not exceed 12%. Conclusion: Camrelizumab is effective and safe in the treatment of patients with digestive system malignancies, but the overall response rate is limited.

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review.

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high‐risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high‐risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis of pancreatic cancer to be applied in the clinic. As the only serum biomarker approved by the United States Food and Drug Administration, carbohydrate antigen 19‐9 (CA19‐9) is not recommended to be used in the early screening of pancreatic cancer because of its limited specificity. Recently, increasing numbers of studies focused on the discovering of novel serum biomarkers and exploring their combination with CA19‐9 in the detection of pancreatic cancer. Besides, the application of liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis are drawing more and more attention. Furthermore, many innovative technologies such as artificial intelligence, computer‐aided diagnosis system, metabolomics technology, ion mobility spectrometry (IMS) associated technologies, and novel nanomaterials have been tested for the early diagnosis of pancreatic cancer and have shown promising prospects. Hence, this review aims to summarize the recent progress in the development of early screening and diagnostic methods, including imaging, pathological examination, serological examination, liquid biopsy, as well as other potential diagnostic strategies for pancreatic cancer.

Role of m6A methylation in occurrence and progression of digestive system malignancies

Role of m6A methylation in occurrence and progression of digestive system malignancies

Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors.

BackgroundThe SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.MethodsThe Oncomine, Ualcan, Kaplan–Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).ResultsIn ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.ConclusionSMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI.

Background: Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD.Methods: A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).Results: Kaplan–Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 [1.031–2.149], P=0.034), CM (adjusted HR = 1.837 [1.141–2.959], P=0.012), MACEs (adjusted HR = 1.257 [1.018–1.551], P=0.033) and MACCEs (adjusted HR = 1.237 [1.029–1.486], P=0.024).Conclusion: An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.

C-kit-negative Extragastrointestinal Stromal Tumor Originating in the Mesentery Misdiagnosed as an Ovarian Tumor before Surgery

Gastrointestinal stromal tumors (GISTs) are rare digestive system malignancies with extragastrointestinal stromal tumors (EGISTs) being even less. Diagnosing GISTs usually requires the identification of c-kit (CD117) expression by immunohistochemical staining. A 53-year-old woman complaining of dyspepsia was referred for the evaluation of a 1.5-cm extrinsic compression at the greater curvature of the proximal antrum. EUS revealed a multiseptated mass with positive Doppler findings. Abdominal CT showed that she harbored a large, 20-cm mass in her abdominal cavity, most likely arising from the right ovary. Surgery revealed a hypervascular tumor arising from the mesentery and attached to the gastric lesser curvature. Pathological examination revealed negativity for c-kit, but positivity for the protein “Discovered on GIST-1” (DOG1), confirming the EGIST diagnosis. Herein, we report this rare case of a c-kit-negative EGIST originating in the mesentery, which was diagnosed based on staining for DOG1.

Repurposing metformin for the treatment of gastrointestinal cancer.

Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies in vitro and in vivo models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.

Prevalence and Determinants of Psychological Distress in Adolescent and Young Adult Patients with Cancer: A Multicenter Survey

Objective:This study aimed to investigate the current prevalence and determinants of psychological distress and the association of distress with general information, character strengths, medical coping, and social support in Chinese adolescents and young adults (AYAs) aged 15–39 years with cancer.Methods:A multicenter survey was carried out. Eight hundred and nine patients completed the Chinese version of the National Comprehensive Cancer Network distress thermometer (DT), the three-dimensional inventory of character strengths, the medical coping modes questionnaire, and the Social Support Rating Scale.Results:The current prevalence of psychological distress in Chinese AYAs with cancer was 83.4%. Binary logistic regression analysis showed that gender, age, educational level, marriage, monthly income, exercise intensity, cancer classifications, treatments, self-control, confrontation, avoidance, and subjective support were all associated with distress. AYA cancer patients who were female, younger, or divorced or had a lower monthly income, education level, or exercise intensity were more likely to have higher level of distress. Compared to AYAs with other cancer classifications, patients with digestive system malignancies, breast cancers, and head and neck malignancies had a higher prevalence of distress. Patients receiving chemotherapy or radiotherapy were more likely to be distressed. The higher the self-control, confrontation, avoidance, and subjective support scores were, the lower the prevalence of distress was among AYA cancer patients.Conclusions:The prevalence of psychological distress in AYA cancer patients was relatively high. Potential interventions targeting exercise intensity, character strengths, medical coping, and social support may decrease the prevalence of psychological distress in this patient population.

Clinical Analysis of Oxaliplatin-related Thrombocytopenia in Patients with Digestive System Malignancy

Clinical Analysis of Oxaliplatin-related Thrombocytopenia in Patients with Digestive System Malignancy

RETRACTED: Thymoquinone sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis via oxidative DNA damage

Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells. Cell viability and IC50 dose for TQ and TRAIL, alone and in combination, were determined using the MTT method. ELISA evaluated the expression levels of 8-Hydroxy-2'-deoxyguanosine. The apoptosis rate was assessed by flow cytometry, ELISA cell death assay, and caspase 8 activity assays. The mRNA and protein evaluation of candidate genes, including survivin, Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP, were accomplished before and after the treatment using qRT-PCR and Western blot analysis, respectively. Our results showed that TQ synergistically increased TRAIL's cell toxic effects as follows: TQ plus TRAIL > TRAIL > TQ. TQ could sensitize the HepG2 cells against the TRAIL-induced apoptosis and amplify the caspase 8 activity. This outcome is achieved by decreasing the mRNA and protein expression levels of anti-apoptotic genes. Our findings suggest that TQ can sensitize the human HCC cell line HepG2 against TRAIL by inducing the death receptor pathway. Moreover, these agents' combinational therapy might promise a therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with HCC.