Inhibitory effect of artemisinin on proliferation and invasion of gastric cancer cells
QIAN Bin1 LI Xiaojun1 CHEN Wei1 YIN Xiaochuan2
1.Department of Pharmacy, First Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650032, China;
2.Department of Cerebral Surgery, First Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650032, China
Abstract:Objective To study the effect of artemisinin on the proliferation and invasion of gastric cancer cells. Methods Human gastric cancer cell line SGC-7901 was cultured and dealt with different doses of artemisinin in serum-free DMEM, respectively as 75, 150, 300 μmol/L artemisinin group, serum-free DMEM without artemisinin as control group. After 48 h of intervention, cell proliferation activity, invasion numbers and mRNA expression of proliferation gene, invasion gene were determined. Results After 48 h of intervention, cell proliferation activity, invasion numbers and Ki-67, CyclinD1, CDK4, CDK6, MMP2, MMP9 mRNA expression of 75, 150, 300 μmol/L artemisinin group were significantly lower than those of control group, TIMP1 and TIMP2 mRNA expression were significantly higher than those of control group (P < 0.05), and the higher the dose of artemisinin, the lower the cell proliferation activity, invasion numbers and Ki-67, CyclinD1, CDK4, CDK6, MMP2, MMP9 mRNA expression, the higher the TIMP1 and TIMP2 mRNA expression (P < 0.05). Conclusion Artemisinin can inhibit the proliferation and invasion of gastric cancer cells by inhibiting the expression of cell cycle proteins and matrix metalloproteinases.
[1] Jomrich G,Schoppmann SF. Targeted therapy in gastric cancer [J]. Eur Surg,2016,48(5):278-284.
[2] Shi WJ,Gao JB. Molecular mechanisms of chemoresistance in gastric cancer [J]. World J Gastrointest Oncol,2016,8(9):673-681.
[3] Jia J,Qin Y,Zhang L,et al. Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis [J]. Mol Med Rep,2016,13(5):4461-4468.
[4] Mondal A,Chatterji U. Artemisinin represses telomerase subunits and induces apoptosis in HPV-39 infected human cervical cancer cells [J]. J Cell Biochem,2015,116(9):1968-1981.
[5] Zhang YJ,Zhan X,Wang L,et al. pH-responsive artemisinin dimer in lipid nanoparticles are effective against human breast cancer in a xenograft model [J]. J Pharm Sci,2015, 104(5):1815-1824.
[6] Abdelfatah E,Kerner Z,Nanda N,et al. Epigenetic therapy in gastrointestinal cancer:the right combination [J]. Therap Adv Gastroenterol,2016,9(4):560-579.
[7] Chang HR,Park HS,Ahn YZ,et al. Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems [J]. BMC Cancer,2016,9(16):200.
[8] Zhou Y,Li W,Xiao Y. Profiling of multiple targets of artemisinin activated by hemin in cancer cell proteome [J]. ACS Chem Biol,2016,11(4):882-888.
[9] Ooko E,Saeed ME,Kadioglu O,et al. Artemisinin derivatives induce iron-dependent cell death(ferroptosis)in tumor cells [J]. Phytomedicine,2015,22(11):1045-1054.
[10] 吴孟轩.青蒿素和顺铂联合干预对胃癌MGC-803细胞株上皮间质转化、血管新生及ATP生成的影响[J].海南医学院学报,2016,22(18):2073-2076.
[11] 王军,赵醒,赵宇阳,等.CyclinD1、CDC25B和p27在胃癌组织中的表达[J].广东医学,2016,37(10):1495-1498.
[12] Matsuhashi N,Takahashi T,Yamaguchi K,et al. The significant role of Cyclin D1 in the synergistic growth-inhibitory effect of combined therapy of Vandetanib with 5-Fluorouracil for gastric cancer [J]. Anticancer Res,2016,36(10):5215-5226.
[13] Kumari S,Puneet,Prasad SB,et al. Cyclin D1 and Cyclin E2 are differentially expressed in gastric cancer [J]. Med Oncol,2016,33(5):40.
[14] 陈超,姚莉敏.胃癌中β-catenin、ki-67和Her-2/Neu表达及对胃癌侵袭、转移的影响[J].重庆医学,2016,45(18):2504-2507.
[15] B■ger C,Behrens HM,R■cken C. Ki67——An unsuitable marker of gastric cancer prognosis unmasks intratumoral heterogeneity [J]. J Surg Oncol,2016,113(1):46-54.
[16] 李波,周烂.血清VEGF、MMP及MK与胃癌术后复发转移的关系研究[J].海南医学院学报,2016,22(9):928-930.
[17] Bornschein J,Seidel T,Langner C,et al. MMP2 and MMP7 at the invasive front of gastric cancer are not associated with mTOR expression [J]. Diagn Pathol,2015,12(10):212.
[18] Kim TH,Jung JY,Roh HJ,et al. Comparative expression of matrix metalloproteinases in internal malignancies and paired cutaneous metastatic lesions [J]. Am J Dermato-pathol,2015,37(5):381-388.
[19] Verma S,Kesh K,Gupta A,et al. An overview of matrix metalloproteinase 9 polymorphism and gastric cancer risk [J]. Asian Pac J Cancer Prev,2015,16(17):7393-7400.
[20] Gurgel DC,Valenca-Junior JT,Dornelas CA,et al. Immunoexpression of metalloproteinases 2 and 14 and TIMP-2 inhibitor in main types of primary gastric carcinomas and lymph node metastasis [J]. Pathol Oncol Res,2015,21(1):73-81.