Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation

Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation
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Neferine 通过 p38 MAPK/JNK 激活诱导人卵巢癌细胞自噬

DOI:
10.1007/s13277-015-4737-8
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发表时间:
2016-01
期刊:
影响因子:
--
通讯作者:
Liu Zhaojian
Liu Zhaojian
中科院分区:
--
文献类型:
--
作者:
Xu Limei;Zhang Xiyu;Li Yinuo;Lu Shuhua;Lu Shan;Li Jieyin;Wang Yuqiong;Tian Xiaoxue;Wei Jian-jun;Shao Changshun;Liu Zhaojian

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卵巢癌是最致命的妇科恶性肿瘤。由于诊断晚、复发、耐药等原因,患者预后较差。寻找新的治疗卵巢癌的药物迫在眉睫。莲子碱是一种从荷花胚中分离得到的双苄基异喹啉类生物碱。在本研究中,我们研究了莲子碱对卵巢癌细胞的抗肿瘤作用。我们发现,莲子碱对人卵巢癌细胞表现出生长抑制作用,而对非恶性输卵管上皮细胞表现出较少的细胞毒性。此外,我们证明了尼古丁诱导自噬并使mTOR通路失活。最后,我们发现p38 MAPK和JNK信号通路都被碱处理激活,并有助于诱导卵巢癌细胞自噬。综上所述,我们的研究结果表明,尼古丁通过激活p38 MAPK/JNK诱导人卵巢癌细胞自噬。莲子碱是一种很有前途的抗卵巢癌药物。
Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.
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