Zhang Xian, Zhou Yong, Gu Ying-Er
Department of Chinese Integrative Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Oncol Lett. 2019 Feb;17(2):1896-1902. doi: 10.3892/ol.2018.9744. Epub 2018 Nov 21.
Ovarian cancer is one of the most common gynecological tumors and is the second most common cause of gynecological cancer-associated mortality worldwide. Tanshinone IIA (Tan-IIA) possesses anticancer activities through inducing the apoptosis of tumor cells. The purpose of the present study was to analyze the ability of Tan-IIA to induce apoptosis of human ovarian cancer cells and , and to examine the potential mechanism underlying its activity. Western blot analysis, immunohistochemistry and flow cytometry were used to analyze the therapeutic effects of Tan-IIA on ovarian cancer. It was demonstrated that Tan-IIA significantly inhibited the growth and aggressiveness of human ovarian cancer cells. Tan-IIA significantly increased the apoptosis of human ovarian cancer cells through cleavage activation of caspases-3, caspase-8 and caspases-9. In addition, Tan-IIA treatment decreased the expression of mitochondrial-protective B-cell lymphoma 2-like protein 2 (Bcl-w) and myeloid cell leukemia-1 long (Mcl-1L) in ovarian cancer cells. Tan-IIA also reduced the expression of phosphoinositide 3-kinase (PI3K), AKT and c-Jun N-terminal kinase (JNK) in human ovarian cancer cells. A specific PI3K inhibitor (LY294002) enhanced the Tan-IIA-inhibited expression of AKT and JNK. The overexpression of PI3K negated the Tan-IIA-inhibited expression of AKT and JNK, and eliminated the Tan-IIA-induced apoptosis of human ovarian cancer cells. Additionally, the assay showed that Tan-IIA treatment inhibited the growth of ovarian cancer through increasing the apoptosis of tumor cells. In conclusion, these findings suggested that the induction of apoptosis by Tan-IIA involves the PI3K/AKT/JNK signaling pathways in ovarian cancer.
卵巢癌是最常见的妇科肿瘤之一，是全球妇科癌症相关死亡的第二大常见原因。丹参酮IIA（Tan-IIA）通过诱导肿瘤细胞凋亡具有抗癌活性。本研究的目的是分析Tan-IIA诱导人卵巢癌细胞凋亡的能力，并研究其活性的潜在机制。采用蛋白质免疫印迹分析、免疫组织化学和流式细胞术分析Tan-IIA对卵巢癌的治疗作用。结果表明，Tan-IIA显著抑制人卵巢癌细胞的生长和侵袭性。Tan-IIA通过激活半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9的切割，显著增加人卵巢癌细胞的凋亡。此外，Tan-IIA处理降低了卵巢癌细胞中线粒体保护蛋白B细胞淋巴瘤2样蛋白2（Bcl-w）和髓样细胞白血病-1长链（Mcl-1L）的表达。Tan-IIA还降低了人卵巢癌细胞中磷酸肌醇3激酶（PI3K）、AKT和c-Jun氨基末端激酶（JNK）的表达。一种特异性PI3K抑制剂（LY294002）增强了Tan-IIA对AKT和JNK表达的抑制作用。PI3K的过表达消除了Tan-IIA对AKT和JNK表达的抑制作用，并消除了Tan-IIA诱导的人卵巢癌细胞凋亡。此外，实验表明Tan-IIA处理通过增加肿瘤细胞凋亡来抑制卵巢癌的生长。总之，这些发现表明Tan-IIA诱导的凋亡涉及卵巢癌中的PI3K/AKT/JNK信号通路。
