Tanshinone IIA induces apoptosis of ovarian cancer cells in vitro and in vivo through attenuation of PI3K/AKT/JNK signaling pathways.
Tanshinone IIA induces apoptosis of ovarian cancer cells in vitro and in vivo through attenuation of PI3K/AKT/JNK signaling pathways.
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DOI：
10.3892/ol.2018.9744
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发表时间：
2018-11
期刊：
影响因子：
2.9
通讯作者：
Xian Zhang;Yong Zhou;Y. Gu
中科院分区：
文献类型：
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作者：
Xian Zhang;Yong Zhou;Y. Gu
卵巢癌是最常见的妇科肿瘤之一，也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而具有抗肿瘤活性。本研究的目的是分析Tan-IIA在体内外诱导人卵巢癌细胞凋亡的能力，并探讨其可能的作用机制。采用Western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能显著抑制人卵巢癌细胞的生长和侵袭性。Tan-IIA通过切割激活caspase-3、caspase-8和caspase-9，显著增加人卵巢癌细胞的凋亡率。此外，Tan-IIA还降低了卵巢癌细胞线粒体保护性B细胞淋巴瘤样蛋白2(Bclw)和髓系细胞白血病1Long(Mcl-1L)的表达。Tan-IIA还可降低人卵巢癌细胞中磷脂酰肌醇3-激酶(PI3K)、AKT和c-jun氨基末端激酶(JNK)的表达。特异性PI3K抑制剂(LY294002)可增强Tan-IIA抑制的AKT和JNK的表达。PI3K的过表达可阻断Tan-IIA抑制的AKT和JNK的表达，消除Tan-IIA诱导的人卵巢癌细胞的凋亡。体内实验表明，Tan-IIA可通过增加肿瘤细胞的凋亡率来抑制卵巢癌细胞的生长。以上结果提示，Tan-IIA诱导卵巢癌细胞凋亡涉及PI3K/AKT/JNK信号通路。
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 in vitro and in vivo, 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 in vivo 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.