Herein, we found that salidroside suppressed hypoxia-inducible factor 1 alpha (HIF-1 alpha) and lysyl oxidase-like protein 2 (LOXL2) within human pancreatic cancer BxPC-3 cells cultured both under normoxia and hypoxia condition. To investigate the effect of salidroside on tumorigenesis of BxPC-3 cells and whether HIF-1 alpha and LXCL2 were involved in this process, cells transfected with or without LOXL2 overexpression vector, were treated with 50 mu g/mL of salidroside or 50 mu M of KC7F2 (a HIF-1 alpha inhibitor) under hypoxia. Cell viability and invasion were assessed using CCK-8 and Transwell chamber assay, respectively. Expression of E-cadherin and matrix metalloproteinase 2/9 (MMP 2/9) was determined, by Western blot analysis, to assess cell mobility at molecular levels. We confirmed that hypoxia increased LOXL2 and induced tumorigenesis of BxPC-3 cells, as evidenced by promoted cell proliferation and invasion, enhanced MMP2/9 while reduced E-cadherin. Interestingly, hypoxia-induced carcinogenesis was significantly retarded by both salidroside and KC7F2, however, enhanced with LOXL2 overexpression. Besides, salidroside and KC7F2 reduced LOXL2, and reversed the tumorigenesis of BxPC-3 cells induced by LOXL2 overexpression. Given the inhibitory effect of salidroside on HIF-1 alpha expression, our data suggested that: (1) LOXL2 was the mechanism, whereby salidroside and KC7F2 showed inhibitory effect on cancer progression of BxPC-3 cells; (2) salidroside exerted its anticancer effect, most likely, by a HIF-1 alpha/LOXL2 pathway. In conclusion, salidroside was a novel therapeutic drug in pancreatic cancer, and downregulation of HIF-1 alpha and LXCL2 was the underlying mechanism.
[1]Shanghai Univ Tradit Chinese Med, Dept Biliary & Pancreat Surg, Baoshan Branch, Shuguang Hosp, 181 Youyi Rd, Shanghai 201900, Peoples R China.
[2]Shanghai Skin Dis Hosp, Dept Hepatol, 1278 Baode Rd, Shanghai 200443, Peoples R China.
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