HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling
HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling
复制标题
HAb18G/CD147 促进肝细胞癌细胞的放射抗性：整合素 beta 1 信号传导的潜在作用
DOI：
10.1158/1535-7163.mct-14-0618
复制
发表时间：
2015-02-01
影响因子：
5.7
通讯作者：
Chen, Zhi-Nan
中科院分区：
文献类型：
--
作者：
Wu, Jiao;Li, Yong;Chen, Zhi-Nan
由于肿瘤放射抵抗的风险，放射治疗在肝细胞癌（HCC）的治疗中发挥了有限的作用。我们实验室先前的研究证实，CD 147与整合素β 1相互作用，在调节HCC细胞的恶性特性中起重要作用。在这项研究中，我们进一步评估了CD 147在肝癌放射抵抗中的作用，并作为提高放射敏感性的潜在靶点。照射后，测定SMMC-7721、CD 147敲除SMMC-7721、HepG 2和CD 147敲除HepG 2细胞的殖民地形成、凋亡、细胞周期分布、迁移和侵袭。采用裸鼠移植瘤模型和肝癌转移模型，检测CD 147在体内放射抵抗中的作用。HAb 18 G/CD 147的缺失可显著增强SMMC-7721和HepG 2细胞的放射敏感性，而HAb 18 G/CD 147的敲除可减弱放射增强的SMMC-7721细胞的迁移和侵袭能力。CD 147的敲除和抗体阻断降低了肝癌细胞在辐射下的肿瘤生长和转移潜力。CD 147缺失的SMMC-7721细胞显示钙蛋白酶、切割的talin、活性整合素β 1水平降低，以及p-FAK（Tyr 397）和p-Akt（Ser 473）水平降低。FAK和PI 3 K抑制剂，以及整合素β 1抗体，增加辐射诱导的SMMC-7721细胞凋亡。我们的数据为CD 147通过调节整合素β 1信号传导作为辐射抗性的重要决定因素提供了证据。抑制HAb 18 G/CD 147整合素的相互作用可能会提高肝癌的放射敏感性，为肝癌的治疗提供一种潜在的新途径。（C）2014年AACR。
Radiotherapy has played a limited role in the treatment of hepatocellular carcinoma (HCC) due to the risk of tumor radioresistance. A previous study in our laboratory confirmed that CD147 interacts with integrin beta 1 and plays an important role in modulating the malignant properties of HCC cells. In this study, we further evaluated the role of CD147 in the radio-resistance of HCC and as a potential target for improving radiosensitivity. Upon irradiation, the colony formation, apoptosis, cell-cycle distribution, migration, and invasion of SMMC-7721, CD147-knockout SMMC-7721, HepG2, and CD147-knockdown HepG2 cells were determined. A nude mouse xenograft model and a metastatic model of HCC were used to detect the role of CD147 in radioresistance in vivo. Deletion of HAb18G/CD147 significantly enhanced the radiosensitivity of SMMC-7721 and HepG2 cells, and knocking out HAb18G/CD147 in SMMC-7721 cells attenuated irradiation-enhanced migration and invasion. The knockout and antibody blockade of CD147 decreased the tumor growth and metastatic potentials of HCC cells under irradiation. CD147 deleted SMMC-7721 cells showed diminished levels of calpain, cleaved talin, active integrin beta 1, and decreased p-FAK (Tyr397) and p-Akt (Ser473) levels. FAK and PI3K inhibitors, as well as integrin beta 1 antibodies, increased the radiation-induced apoptosis of SMMC-7721 cells. Our data provide evidence for CD147 as an important determinant of radioresistance via the regulation of integrin beta 1 signaling. Inhibition of the HAb18G/CD147 integrin interaction may improve the efficiency of radiosensitivity and provide a potential new approach for HCC therapy. (C)2014 AACR.