Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.
Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.
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ADAM9 的过表达通过激活自噬降低肝细胞癌细胞的放射敏感性。
DOI：
10.1080/21655979.2021.1965694
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Zhu L;Zhao Y;Yu L;He X;Wang Y;Jiang P;Yu R;Li W;Dong B;Wang X;Dong Y
崩解素和金属蛋白酶（ADAM）9在人肝细胞癌（HCC）细胞中上调，但其对HCC放射敏感性的影响尚不清楚。本研究旨在研究ADAM9对HCC放射敏感性的影响，并揭示其可能的机制，这可能有助于确定潜在的治疗策略。采用western blot、qRT-PCR和免疫荧光法检测x射线照射后ADAM9的表达变化。采用慢病毒包装技术构建了ADAM9稳定敲低和过表达细胞系。通过CCK-8实验、皮下肿瘤发生实验和克隆形成实验检测ADAM9表达改变的HCC细胞的放射敏感性。本研究还确定了自噬如何影响HCC细胞的放射敏感性。通过免疫组化检测放疗后切除的HCC组织中ADAM9、p62、Bax的表达，并统计分析这些分子水平之间的关系。x线照射后肝癌细胞adam9表达水平升高。本工作通过CCK-8实验、皮下肿瘤发生实验、克隆形成实验发现，ADAM9敲低后MHCC97H细胞放射敏感性升高，而过表达ADAM9后Huh7细胞放射敏感性降低。此外，ADAM9通过下调Nrf2表达诱导HCC细胞自噬，而自噬抑制或诱导逆转了ADAM9表达改变对放射敏感性的影响。放疗后肝癌组织中ADAM9水平与Bax、p62表达呈负相关。综上所述，ADAM9降低了HCC细胞的放射敏感性，而自噬介导了这一过程。
A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.
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影响因子：
2.7
作者：
Li, Sirui;Shi, Dan;Cheng, Guanghui
通讯作者：
Cheng, Guanghui
影响因子：
13.5
作者：
Kohga, Keisuke;Takehara, Tetsuo;Hayashi, Norio
通讯作者：
Hayashi, Norio
DOI：
10.31557/apjcp.2019.20.12.3679
发表时间：
2019-12-01
期刊：
Asian Pacific journal of cancer prevention : APJCP
影响因子：
--
作者：
Assani, Ganiou;Segbo, Julien;Zhou, Yunfeng
通讯作者：
Zhou, Yunfeng
影响因子：
5.7
作者：
Kim JM;Jeung HC;Rha SY;Yu EJ;Kim TS;Shin YK;Zhang X;Park KH;Park SW;Chung HC;Powis G
通讯作者：
Powis G
影响因子：
3.5
作者：
Kudo, Masatoshi
通讯作者：
Kudo, Masatoshi