Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

作者：Dong, Gang; Zheng, Qiong-Dan; Ma, Min; Wu, Si-Fan; Zhang, Rui; Yao, Rong-Rong; Dong, Yin-Ying; Ma, Hui; Gao, Dong-Mei; Ye, Sheng-Long; Cui, Jie-Feng; Ren, Zheng-Gang; Chen, Rong-Xin^*

来源：Cancer Medicine, 2018, 7(3): 820-830.

DOI：10.1002/cam4.1330

• Angiogenesis
• GDF15
• hepatocellular carcinoma
• thalidomide
• transarterial chemoembolization

Transarterial chemoembolization (TACE) is the standard treatment for unresectable hepatocellular carcinoma (HCC). Hypoxia-induced angiogenesis by TACE is linked to treatment failure; however, whether the chemotherapeutic damage of TACE to HCC could increase tumor angiogenesis has not been explored. The molecular effects of chemotherapy-damaged HCC cells on the neo-angiogenesis were investigated in vitro and in vivo. The expression of growth differentiation factor 15 (GDF15) was significantly upregulated in HCC cells exposed to chemotherapeutic agents. GDF15 from chemotherapy-damaged HCC cells promoted the in vitro proliferation, migration, and tube formation of endothelial cells. The pro-angiogenic effect of GDF15 was through the activation of Src and its downstream AKT, MAPK, and NF-kappa B signaling, which was blocked by thalidomide. The use of thalidomide significantly attenuated the in vivo chemotherapy-damaged HCC cells-promoted angiogenesis in nude mice. In conclusion, the chemotherapeutic damage in TACE to HCC could promote tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro-angiogenic effects.

• 出版日期2018-3
• 单位复旦大学