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mTOR activation is critical for betulin treatment in renal cell carcinoma cells.

Abstract：

:Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner. Furthermore, betulin treatment decreases the levels of glucose consumption and lactate production in 786-O cells, while minimal effects were observed in Caki-2 cells. In addition, betulin significantly inhibited the expression of PKM2 and HK2 in 786-O cells. Finally, knockdown of PKM2 or HK2 in 786-O reversed the anti-proliferative effects of betulin, and overexpression of PKM2 or HK2 in Caki-2 cells enhanced the sensitivity to betulin treatment. Taken together, these findings demonstrated the critical role of mTOR activation in RCC cells to betulin treatment, suggesting that betulin might be valuable for targeted therapies in RCC patients with mTOR activation.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Cheng W,Ji S,Zhang H,Han Z,Liu Q,Wang J,Ping H

doi

10.1016/j.bbrc.2016.11.153

subject

Has Abstract

pub_date

2017-01-22 00:00:00

pages

1030-1036

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)32027-7

journal_volume

482

pub_type

杂志文章

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