Integrin beta-8 (ITGB8) silencing reverses gefitinib resistance of human hepatic cancer HepG2/G cell line.
Hepatic cancer is a class of cancer that is relatively insensitive to chemotherapy, and cancers that harbor EGFR active mutations are more sensitive to EGFR-TK inhibitor such as gefitinib, which becomes the first-line treatment of this subtype of cancer. However, almost all patients treated with gefitinib will develop drug resistance. Here we show that a protein called integrin beta-8 (ITGB8) when over-expressed, is correlated with the gefitinib resistance of hepatic cancer cell line HepG2/G. After ITGB8 silencing, the drug resistance is reversed as the cell proliferation decreases and apoptosis rate increases significantly by gefitinib treatment when compared to HepG2/G. We demonstrated that multi-drug resistant proteins ABCB1, ABCC2 and ABCG2, anti-apoptosis proteins like survivin and Bcl-2, and cycle promoting protein CDK1 are involved in drug resistance of HepG2/G. Other drug-resistance relative proteins like SOD, GST, TS and HIF-1 are also modulated by ITGB8 silencing, but their role in this gefitinib resistance might be indirect. TGF beta pathway could be a critical pathway by which ITGB8 modulates the sensitivity of HepG2/G to gefitinib.
Department of Emergency, Tianjin First Central Hospital Tianjin 300192 China.
Wei-Wei
WW
Wang
Institute of Infectious Diseases, The Second Hospital of Tianjin Medical University Tianjin 300211 China.
Yu-Bao
YB
Wang
Department of Integration of Traditional Chinese and Western Medicine, Tianjin First Central Hospital Tianjin 300192 China.
Dong-Qiang
DQ
Wang
Department of Intensive Care Unit, Tianjin First Central Hospital Tianjin 300192 China.
Zhu
Z
Lin
Internal Medicine Department, Tianjin Occupational Disease Prevention Hospital Tianjin 300020 China.
Ren-Jun
RJ
Sun
Hepatic cancer; gefitinib resistance; integrin beta-8