doi: 10.5732/cjc.011.10383

YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition

Ying Cheng, Wei Li, Ying Liu, Huan-Chen Cheng, Jun Ma, Lin Qiu

Jilin Tumor Hospital， Changchun， Jilin 130012， P. R.China

[Abstract] 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), the hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor, suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions. Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions. In the current study, we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells. In the in vitro experiments, we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia. Under normoxic conditions, YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G1 phase, and these effects were possibly related to caspase 8, p21, and p27 expression. RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions, but suppressed the expression of epidermal growth factor receptor(EGFR) at the mRNA and protein levels under normoxic conditions. In vivo, YC-1 prolonged survival, increased survival rate, decreased tumor size and metastasis rate, and inhibited tissue EGFR and HIF-1α expression. However, YC-1 exerted no obvious effect on body weight. These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects. Thus, YC-1 is a promising target drug for breast cancer.

Chinese Journal of Cancer 2012, Volume: 31, Issue 5, Page: 248-256

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Ying Cheng, Wei Li, Ying Liu, Huan-Chen Cheng, Jun Ma, Lin Qiu. YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition. Chin J Cancer. 2012, 31(5):248-256. doi:10.5732/cjc.011.10383


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