Carbon Ion Induces Cell Death and G2/M Arrest Through pRb/E2F1Chk2/Cdc2 Signaling Pathway in X-ray Resistant B16F10 Melanoma Cells

碳离子通过 pRb/E2F1Chk2/Cdc2 信号通路诱导抗 X 射线 B16F10 黑色素瘤细胞死亡和 G2/M 停滞

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作者:Sha Li, Hefa Huang, Mengjie Xing, Jin Qin, Hong Zhang, Yang Liu, Liping Zhang, Chao Zhang, Zhongze Tian, Xingxin Gao, Rui Zhao, Aihong Mao

Abstract

To explore the effect of high-LET carbon ion (C-ion) radiation on malignant melanoma, we systematically compared the radiobiological effects of C-ion with that of X-rays in B16F10 melanoma cells. Results showed that C-ion radiation statistically inhibited clonogenic survival capacity of B16F10 melanoma cells. The RBE was 3.7 at D 10 levels, meaning 1.0 Gy C-ion should cause the same biological effect as ≥ 3.0 Gy X-rays. In addition, we also observed a stronger proliferation-inhibiting and higher ratio of cell apoptosis and necrosis in B16F10 cells treated with C-ion than X-rays. Moreover, C-ion radiation exhibited stronger and long-lasting G2/M arrest than X-rays. As an underlying mechanism, we speculated that C-ion radiation-induced G2/M block through activating pRb/E2F1/Chk2 pathway. With these results, we highlighted the potential of C-ion in treatment of cutaneous melanoma. Further, in vitro experiments as well as clinical trials are needed to further evaluate the effect of carbon ion radiotherapy in melanoma.

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