Miyata Miwa, Morishita Asahiro, Sakamoto Teppei, Katsura Akiko, Kato Kiyohito, Nishioka Tomoko, Toyota Yuka, Fujita Koji, Maeda Emiko, Nomura Takako, Tani Joji, Miyoshi Hisaaki, Yoneyama Hirohito, Kobara Hideki, Fujiwara Shintaro, Nishiyama Noriko, Iwama Hisakazu, Himoto Takashi, Hirashima Mitsuomi, Masaki Tsutomu
Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Life Science Research Center, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Int J Oncol. 2015 Aug;47(2):535-42. doi: 10.3892/ijo.2015.3036. Epub 2015 Jun 5.
Cisplatin [cis-diamminedichloroplatinum (II)], is a platinum coordination compound that is commonly used to treat hepatocellular carcinoma (HCC). It is also one of the most compelling anticancer drugs. Recent studies suggest that cisplatin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of cisplatin in several types of cancers, including HCC, has not been elucidated. The goal of the present study was to evaluate the effects of cisplatin on the proliferation of HCC cells in vitro and to determine which microRNAs (miRNAs) are associated with the anticancer effects of cisplatin in vitro. We used various human HCC-derived cell lines to study the effects of cisplatin on human HCC cells. Cisplatin led to a strong dose- and time- dependent inhibition of cell proliferation in HLE, HLF, HuH7, Li-7, Hep3B and HepG2 cells in vitro. Cisplatin also blocked the progression of the cell cycle in the G0/G1 phase, which inhibited cyclin D1 and induced apoptosis. In addition, miRNA expression was markedly altered by treatment with cisplatin in vitro. Therefore, various miRNAs induced by cisplatin may also contribute to the suppression of cellular proliferation and apoptosis. Our results demonstrate that cisplatin inhibits the growth of HCC, possibly through the induction of G1 cell cycle arrest and apoptosis through the alteration of microRNA expression.
顺铂[顺式二氨基二氯铂(II)]是一种铂配位化合物，常用于治疗肝细胞癌(HCC)。它也是最具说服力的抗癌药物之一。最近的研究表明，顺铂可能降低癌症风险并改善预后。然而，顺铂在包括HCC在内的几种癌症中的抗肿瘤机制尚未阐明。本研究的目的是评估顺铂对体外HCC细胞增殖的影响，并确定哪些微小RNA(miRNA)与顺铂在体外的抗癌作用相关。我们使用了各种源自人HCC的细胞系来研究顺铂对人HCC细胞的影响。顺铂在体外对HLE、HLF、HuH7、Li-7、Hep3B和HepG2细胞的细胞增殖产生了强烈的剂量和时间依赖性抑制。顺铂还阻断了细胞周期在G0/G1期的进程，抑制了细胞周期蛋白D1并诱导了细胞凋亡。此外，体外顺铂处理显著改变了miRNA表达。因此，顺铂诱导的各种miRNA也可能有助于抑制细胞增殖和凋亡。我们的结果表明，顺铂可能通过诱导G1期细胞周期停滞和通过改变微小RNA表达诱导凋亡来抑制HCC的生长。
