RUNX3 inhibits growth of HCC cells and HCC xenografts in mice in combination with adriamycin.
Here, we report that a loss or decrease of RUNX3 expression was found in 73 cases of HCCs as compared with that in normal liver tissues (p < 0.001). Various human HCC cell lines also exhibited loss or decrease of RUNX3 expression. The introduction of RUNX3 by an adenovirus vector into HCC cell lines which had decreased expressions of RUNX3 inhibited cell proliferation and cell cycle progression, decreased anchorage-independent growth, and inhibited tumorigenesis in nude mice. Exogenous expression of RUNX3 sensitized HCC cells to cytotoxic drugs and to apoptosis induced by chemotherapeutic drug adriamycin in vitro. Ectopic expression of RUNX3 in HCC cells enhanced caspase-8 and decreased Bcl-2 expression. Treatment of nude mice bearing subcutaneously established HCC tumors with a combination of an adenovirus expressing RUNX3 and adriamycin completely suppressed tumor growth. In conclusion, overexpression of RUNX3 might be a promising candidate as a treatment for HCC that would increase sensitivity to chemotherapeutic drugs.
Li
Xiaohua
X
State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Zhang
Ying
Y
Zhang
Yafei
Y
Qiao
Taidong
T
Wu
Kaichun
K
Ding
Jie
J
Liu
Jie
J
Fan
Daiming
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D050677:Core Binding Factor Alpha 3 Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D004317:Doxorubicin