Regulation Of HSP27 In Cisplatin-sensitivity In Gastric Cancer Cells

Background: Gastric cancer is the fifth most common cancer and second cause of cancer-related death in the world.Radical surgery,chemotherapy and radiotherapy are the conventional method in treating it.There are about 400 thousand newly-diagnosed gastric cancer patients in China each year,but most of them are advanced gastric cancer.Patients with advanced gastric cancer need preoperative neoadjuvant chemotherapy and postoperative chemotherapy to reduce postoperative recurrence and metastasis and to improve the long-term survival of the patients.However,only 50% of the patients were sensitive to the initial chemotherapy,and some of them gradually develop resistance to chemotherapy.The emergence of drug resistance has obviously influenced the curative effect of chemotherapy.Therefore,elucidating the molecular mechanism of gastric cancer chemotherapy resistance and reversing chemotherapy resistance of gastric cancer cells is one of the important measures to improve the chemotherapy efficacy of gastric cancer.Platinum drugs are the basic drugs for chemotherapy of gastric cancer,including carboplatin,oxaliplatin and cisplatin.Cisplatin can improve the patient’s symptoms and prolong the median survival of the cancer patients by destroying the DNA synthesis in tumor cells.However,after many years of clinical application,cisplatin resistance of gastric cancer has become the main reason for limiting its clinical application.As an ATP-independent chaperone,several studies have also shown Heat shock protein 27(HSP27)overexpressed in some human carcinomas arising from prostate,breast,stomach,cervix.High level of HSP27 is also linked to cancer progression,poor prognosis,resistance to chemotherapy.Recently,several studies have found that HSP27 plays a key role in cell autophagy.Autophagy,a basic lysosome process,degrade organelles and proteins to produce energy to maintain cell homeostasis.A number of studies have shown that cell autophagy contributes to cancer resistance.However,there is no report on whether HSP27 is involved in cisplatin resistance and cell autophagy in gastric cancer cells.Objective : This study will preliminarily study the role of HSP27 in cisplatin resistance and cell autophagy in gastric cancer cells.Methods: 1.Gastric cancer cell lines BGC823,SGC7901 were treated with cisplatin for 12 and 24 hours and then the expression of HSP27 was detected by Western blotting and PCR.2.BGC823 and SGC7901 cells were transfected with control sh RNA or HSP si RNA and then those cells were treated with cisplatin for 24 hours.After that cell viability was analyzed by CCK-8 kit.3.SGC7901 cells were treated with different concentrations of cisplatin(0ug/ml,3ug/ml,6ug/ml,12ug/ml,24ug/ml,48ug/ml)for 24 hours and then detected the level of LC3II(autophagy marker protein)by Western blotting.BGC823 and SGC7901 cells were transfected with control si RNA and Hsp27 si RNA and then treated with cisplatin for 24 hours.The level of LC3 II was analyzed by Western blotting.Results: 1.cisplatin promoted obviously enhanced expression of HSP27 in the human gastric cancer cell lines,SGC7901,BGC823.Moreover,this effect was time dependen.2.Transfection the si RNA of HSP27 into BGC823 and SGC7901 cells made them significantly more sensitive to cisplatin.3.During a certain concentration range,cispaltin can promote the expression of LC3II(autophagy marker protein)in gastric cancer cell SGC7901.However,inhibition of HSP27 could reverse the increase of LC3 II induced by cisplatin in gastric cancer cells.However,knockdown of HSP27 promote autophagy in gastric cancer cells untreated with cisplatin.Conclusion : cisplatin promotes the expression of HSP27 in gastric cancer cells.Inhibition of HSP27 increases the sensitivity of gastric cancer cells to cisplatin.HSP27 regulates the autophagy in gastric cancer cells during chemotherapy.