JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (5): 31-35.doi: 10.6040/j.issn.1671-7554.0.2016.1293

Previous Articles     Next Articles

Effects of salinomycin combined with cisplatin on the proliferation and apoptosis of human gastric cancer cell line MKN-45

ZHAO Ming1,2,3, NIU Jie1, LI Fangqin3, WANG Aihong1,2, PANG Qiuxia1,2, CHEN Meini1,2, ZHOU Lizhen1, ZHAO Jumei1,2   

  1. 1. Medical College of Yanan University, Yanan 716000, Shaanxi, China;
    2. Key Laboratory of the Prevention and Treatment of Tumor, Yanan 716000, Shaanxi, China;
    3. Clinical laboratory of Affiliated Hospital of Yanan University, Yanan 716000, Shaanxi, China
  • Received:2016-10-12 Online:2017-05-10 Published:2017-05-10

PDF (PC)

220

Abstract: Objective To investigate the effects and mechanisms of salinomycin(Sal)combined with cisplatin on the proliferation and apoptosis of human gastric cancer cell line MKN-45. Methods MKN-45 cells were cultured in vitro to logarithmic growth phase, and the proliferation rate of cell line MKN-45 preprocessed separately and jointly by Sal and cisplatin was detected with methyl thiazolyltetrazolium(MTT)method. The apoptosis were examined by AO/EB apoptosis kit and the protein expression levels of NF-κB and caspase-3 were detected with Western blotting. Results MTT assay indicated that the apoptosis rate of MKN-45 cells treated by the combination by Sal and cisplatin was obviously more than that by Sal and cisplatin used separately(P<0.05). AO/EB showed that administration of Sal and cisplatin respectively the apoptotic morphology was obvious compared with that of the control group, and the combined effect of the two drugs was more significant. Western blotting result showed that, after the Sal and cisplatin used in combination, the protein of NF-κB expression level decreased(P<0.05)and the protein caspase-3 increased(P< 山 东 大 学 学 报 (医 学 版)55卷5期 -赵明,等.盐霉素联合顺铂对人胃癌细胞MKN-45增殖和凋亡的影响 \=-0.05). Conclusion Sal suppresses gastric cancer cell proliferation, and combination of Sal with cisplatin would enhance the effect cisplatin does. The mechanism may be inhibiting the activation of NF-κB and up-regulation of the caspase-3 apoptotic gene in the downstream.

Key words: Salinomycin, Cisplatin, MKN-45, NF-κB, Caspase-3

CLC Number: 

  • R735.2
[1] 邹文斌, 李兆申. 中国胃癌发病率及死亡率研究进展[J].中国实用内科杂志, 2014, 34(4): 408-415.
[2] Verdoodt B, Vogt M, Schmitz I, et al. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species[J]. PLoS One, 2012, 7(9): e44132. doi: 10.1371/journal.pone.0044132.
[3] Lu D, Choi MY, Yu J, et al. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells[J]. Proc Natl Acad Sci U S A, 2011, 108(32): 13253-13257.
[4] Lee HG, Shin SJ, Chung HW, et al. Salinomycin reduces stemness and induce apoptosis on human ovarian cancer stem cell[J]. J Gynecol Oncol, 2016,14: e14. doi:10.3802/jgo.2017.28. e14.
[5] Kloaw J, Eissele J, Volz C, et al. Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells[J]. BMC Cancer, 2016, 16(1): 896. doi:10.1186/s12885-016-2879-8.
[6] Gong Z, Chen D, Xie F, et al. Codelivery of salinomycin and doxorubicin using nanoliposomes for targeting both liver cancercells and cancer stem cells[J]. Nanomedicine(Lond), 2016, 11(19): 2565-2579.
[7] Ko JC, Zheng HY, Chen WC, et al. Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression[J]. Biochem Pharmacol, 2016, 122: 90-98. doi: 10.1016/j.bcp.2016.09.022.
[8] Roulston GD, Burt CL, Kettyle LM, et al. Low-dose salinomycin induces anti-leukemic responses in AML and MLL[J]. Oncotarget, 2016, 7(45): 73448-73461.
[9] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[10] 陈万青, 郑荣寿, 张思维, 等. 2012年中国恶性肿瘤发病和死亡分析[J].中国肿瘤, 2016, 25(1): 1-8. CHEN Wanqing, ZHENG Rongshou, ZHANG Siwei, et al. Report of cancer incidence and mortality in China, 2012[J]. China Cancer, 2016, 25(1): 1-8.
[11] Miyazaki Y, Shibuya M, Sugawara H, et al. Salinomycin, a new polyether antibiotic[J]. J Antibiotics, 1974, 27(11): 814-821.
[12] Naujokat C, Fuchs D, Opelz G. Salinomycin in cancer: a new mission for an old agent[J]. Mol Med Rep, 2010, 3(4): 555-559.
[13] Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening[J]. Cell, 2009, 138(4): 645-659.
[14] Chung H, Kim YH, Kwon M, et al. The effect of salinomycin on ovarian cancer stem-like cells[J]. Obstet Gynecol Sci, 2016, 59(4):261-268.
[15] Schenk M, Aykut B, Teske C, et al. Salinomycin inhibits growth of pancreatic cancer and cancer cell migration by disruption of actin stress fiber integrity[J]. Cancer Letters, 2015, 358(2): 161-169.
[16] 吴丹心, 陈可绪, 陈冬杰, 等. 盐霉素联合ApoG2诱导鼻咽癌CNE-2细胞凋亡的实验研究[J]. 实用医学杂志, 2014, 30(19): 3062-3065.
[17] Li T, Su L, Zhong N, et al. Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells[J]. Autophagy, 2013, 9(7): 1057-1068.
[18] Kopp F, Hermawan A, Oak PS, et al. Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration [J]. Molecular Cancer, 2014, 13: 16. doi: 10.1186/1476-4598-13-16.
[19] Wang Y. Effects of salinomycin on cancer stem cell in human lung adenocarcinoma A549 cells [J]. Med Chem, 2011, 7(2): 106-111.
[20] Kucharczak J, Simmons MJ, Fan Y, et al. To be or not to be: NF-kappa B is the answer—role of Rel/NF-kappa B in the regulation of apoptosis[J]. Oncogene, 2004, 22(56): 8961-8982.
[21] Perkins ND. The diverse and complex roles of NF-κB subunits in cancer[J]. Nat Rev Cancer, 2012, 12(2): 121-132.
[22] Karin M. Nuclear factor-kappa B in cancer development and progression[J]. Nature, 2006, 441(7092): 431-436.
[23] Oiso S, Ikeda R, Nakamura K,et al. Involvement of NF-κB activation in the cisplatin resistance of human epidermoid carcinoma KCP-4 cells[J]. Oncol Rep, 2012, 28(1): 27-32.
[24] Takemoto S, Yamamoto T, Tsuru K, et al. Platelet adhesion on titanium oxide gels: effect of surface oxidation[J]. Biomaterials, 2004, 25(17): 3485-3492.
[25] 董雅洁,高维娟. bcl-2、bax、caspase-3在细胞凋亡中的作用及其关系[J]. 中国老年学杂志, 2012, 32(21): 4828-4830.
[1] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1-6.
[2] ZHANG Nan, ZHOU Lixiao, SUN Chenglin. Protective effect of riluzole on the damage of rat retina induced by acute intraocular hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(8): 27-31.
[3] CUI Yong, ZHANG Rongxiang, WANG Fuli, WANG Guoying, FENG Jianlin, ZHANG Haixia. Clinical efficacy of BSD2000 deep hyperthermia combined with chemotherapy of TP regimen for advanced ovarian cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(7): 53-57.
[4] YU Xin, LIU Xiaojing, LIU Xiangqun. The inhibitory effect of baicalin on endothelial cell apoptosis induced by ox-LDL [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 5-9.
[5] TU Yunhua, KANG Yingqian, ZHOU Ying, YE Zhenyuan, XUE Yuecui, DENG Renyuan, WANG Meizhu, CHEN Lan, CAO Yu. Effect of turmeric volatile oil on the proliferation and apoptosis of human leukemia cell line THP-1 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 46-51.
[6] LIU Jie, LIU Jinzhi, LIN Yan, HUANG Zhan, WANG Aihua. Effects of thrombolytic therapy with broadened therapeutic window on the free radical activity and the expression of Caspase-3 in a rat model of acute cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 26-30.
[7] YANG Lu, LIU Yanguo, LI Jisheng, WANG Xiuwen. Effect of bufalin on chemosensitivity to cisplatin in non-small cell lung cancer and the underlying mechanisms [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 6-11.
[8] LI Mei, MENG Qinghui, CAI Qiaoying, XU Yan, FAN Xiaoting. Effect of acetylpuerarin on the expression of caspase-3 in BV-2 microglia induced by Aβ25-35 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(10): 32-36.
[9] XIA Haimiao, SUI Rubo, ZHANG Lei, LIU Dandan. Morphological changes and expressions of cleaved Caspase-3, PARP-1 in cerebellar fastigial nucleus of rats with vascular dementia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(8): 34-38.
[10] ZHANG Min, WANG Xuefeng. Killing effect of apoptotic-tumor-cell-loaded dendritic cells on laryngeal carcinoma cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(7): 32-36.
[11] WANG Miaomiao1, DIAO Xueqin2, ZHUANG Yunlong3, XU Gang4, ZHOU Nan1, JIA Yanglei1, LI Mengmeng1, REN Guijie1. Effects of puromycin-sensitive aminopeptidase on the apoptosis induced by TauP301L in the cultured cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 1-7.
[12] WEN Min1, ZHAO Jing2, BAO Xing-xing3, DENG Cheng-min4, TONG Xue-tao3. Expression of the apoptosis-related protein in prefrontal cortex in a rat model of autism [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(2): 48-51.
[13] LIU Yuanyuan, WANG Yifei, ZHANG Chunmin, LIU Yao, WEI Guo, ZHANG Chunhong, LIU Ying. Effects of ALA-PDT on Caspase-3 and Caspase-7 expressions in cutaneous squamous cell carcinoma A431 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(12): 50-53.
[14] SUN Xiu-mei1, GAO Feng2, LIU Zi-feng3. Inhibition of Salinomycin on the characteristics of colon cancer stem cell [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(9): 40-44.
[15] ALIMUJIANG·Stiwaerdi, ZHANG Tao, PATIGULI·Aerxiding, LIU Li. Clinical analysis of recombinant human endostatin combined with gemcitabine and  cisplatin therapy in advanced non-small cell lung cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 95-98.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd