Panax Notoginseng Saponins Reduces The Cisplatin-Induced Acute Renal Injury By Increasing Hif-1 Alpha/Bnip3 To Inhibit Mitochondrial Apoptosis Pathway

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1 alpha in the rat model, according to the data from our previous works. However, the underlying link between HIF-1 alpha and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1 alpha-dependent apoptosis. A stably HIF-1 alpha-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1 alpha-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1 alpha and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1 alpha-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1 alpha-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1 alpha-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1 alpha to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.