IL-6 is involved in malignancy and doxorubicin sensitivity of renal carcinoma cells.
Various survival factors such as the pleiotropic cytokine interleukin-6 (IL-6), a major mediator of inflammation and activator of signal transducer and activator of transcription 3 (STAT3), serve to block apoptosis in cancer cells. Our present study revealed that the expression of IL-6, while not other IL-2, IL-4, IL-8, or IL-10, was significantly elevated in resistance of renal carcinoma cells (RCC) when compared with human renal proximal tubule epithelial cell line HK-2. The inhibition of IL-6 by siRNA can suppress the proliferation, migration and invasion of RCC cells and increase the doxorubicin (Dox) sensitivity. While recombination IL-6 can attenuate the inhibition effects of Dox on proliferation of RCC cells. Further studies indicated that inhibition of IL-6 by siRNA can decrease the phosphorylation of STAT3 in RCC cells. Over expression of STAT3 increased the proliferation, migration and invasion of RCC cells and reversed si-IL-6 induced increase of Dox sensitivity of ACHN and A498 cells. In addition, IL-6 treatment can activate ERK1/2 via increasing its phosphorylation. PD98059, the ERK1/2 inhibitor, attenuated IL-6 induced proliferation and synergistically increased the Dox sensitivity of si-IL-6 transfected ACHN cells. Collectively, our data suggested that IL-6 plays an important role in malignancy and Dox sensitivity of RCC. The targeted inhibition of IL-6 signals might be a promising therapeutic strategy for the treatment of renal cancer.
a Department of Neurology , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Yanqiang
Y
Chen
b Department of Urology , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Jianzhen
J
Liu
c Department of Nephrology , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Pei
P
Lv
d Cardiovascular Department , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Jiangyan
J
Gao
e Department of Thoracic Surgery , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Mingzheng
M
Wang
d Cardiovascular Department , Hebei Chest Hospital , Shijiazhuang , Hebei , China.
Yongjun
Y
Wang
D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D004317:Doxorubicin
Dox; ERK1/2; IL-6; STAT3; renal cancer