Study Of Peiminine On Enhancing Chemotherapy Sensitivity On Gastric Cancer And Its Mechanism

Objective:Gastric cancer?GC?is one of the most common malignancy of digestive tract,being the second leading cause of cancer-related death worldwide and the 5-years survival rate of patients relatively low.What's more,the early diagnosis rate of gastric cancer is low.The patients with moderate advanced gastrointestinal cancer are often treated with traditional Chinese medicine combined with chemotherapy,it obviously reduces toxicity and increases the quality of patient's life.Compared with using chemotherapy alone,the treatment of gastric cancer by Chinese medicine combined with chemotherapy has obvious benefit in the remission rate,improvement rate,quality of life and the survival rate of 3 years to 5 years.The main content of this study is to investigate the effect of peiminine on enhancing chemotherapy sensitivity on gastric cancer and its mechanism.Methods:?1?In vitro growth inhibition and drug sensitivity of peiminine were assayed by MTT.?2?Flow cytometry was used to determine the drug-induced apoptosis rate.?3?Transplanted tumor model in nude mice was used to detect the chemotherapeutic drug sensitivity in vivo.Draw the tumor growth-curve of tumor volume according time in each group.Then the heavy tumor inhibitory rate was calculated.?4?Western Blotting was used to examine the expression of CyclinD1,cl-PARP.And the RayBio^?Human RTK Phosphorylation Antibody Array Kit was used to test the differential protein expression.Results:?1?50?M of peiminine was used as the optimal concentration based on viability results for avirulence dose.Peiminine enhanced the chemotherapeutic drug sensitivity and decreased the value of IC₅₀ in gastric cancer cell lines.?2?Peiminine and Adriamycin combinations induced apoptosis in gastric cancer.The apoptosis rate in combinations group is 55.4%,and the rate of using Adriamycin group is less than 20%.?3?Peiminine enhanced the tumor growth inhibitory activity of Adriamycin in vivo.Compared with the control group,the combinations of two drugs inhibition the tumor weight at 68.75%?**p<0.01?,while Adriamycin group caused a18.75%suppression.?4?The expression of CyclinD1 was decreased and the level of cl-PARP was increased after peiminine combined with Adriamycin,according to the result of RayBio^?Human RTK Phosphorylation Antibody Array Kit,most of phosphorylation of receptor tyrosine kinases were low expression in two drugs combinations.The expression of P-EGFR and P-FAK were downregulated in combinations group,and the validation of P-EGFR and P-FAK were in accordance with the result of Phosphorylation Antibody Array Kit.Conclusion:Our research indicated that peiminine maybe a new chemosensitizer through inhibiting the proliferation and inducing the apoptosis to enhance the chemotherapeutic drug sensitivity of Adriamycin in gastric cancer.