Preadipocyte Promotes Cell Invasion Of Prostate Cancer By CAMKK2

Objectives: Obesity is one of the most important risk factors for prostate cancer.A large number of studies have shown that the increase of BMI is closely related to the increase of the risk of prostate cancer.However,the mechanism of preadipocytes on the occurrence of prostate cancer is still unclear.This study intends to explore the effect of preadipocytes on invasiveness of prostate cancer cells and its regulatory mechanism.Methods: A co-culture system of preadipocytes and prostate cancer cells was established.Transwell invasion test was used to detect the effect of preadipocytes on the invasion ability of prostate cancer cells,and the effect of preadipocytes on the invasion ability of prostate cancer cells after inhibiting CAMKK2 and AMPK pathways was detected.The mRNA expression of CAMKK2 in prostate cancer cells DU145 and 22RV1 was detected by qRT-PCR,and the effect of inhibition of CAMKK2 on the expression of AMPK pathway in prostate cancer cells was detected by Western blot.Results: Pre-adipocyte 3T3L1 can promote the invasion of prostate cancer cells DU145 and 22RV1(P < 0.01),and can increase the expression level of CAMKK2 in prostate cancer cells(P < 0.01).The co-culture model found that preadipocytes can reverse the inhibitory effect of STO-609 on CAMKK2(P < 0.05).After AMPK inhibitor was added to the co-culture model,Transwell experiment showed that the effect of preadipocytes on the invasiveness of prostate cancer cells was weakened(P < 0.05).After inhibition of CAMKK2,the enhancement of invasiveness of prostate cancer cells by preadipocytes is inhibited.The addition of CAMKK2 inhibitor after 3T3-L1 co-culture with prostate cancer cells can inhibit the activation of AMPK pathway and down-regulate the expression of p-AMPK(P < 0.05).AMPK pathway can affect the invasiveness of preadipocytes to prostate cancer cells.Conclusions: Preadipocytes may promote the invasiveness of prostate cancer cells by up-regulating the expression of CAMKK2,and the effect of up-regulating CAMKK2 by preadipocytes on the invasiveness of prostate cancer cells may be realized by participating in the regulation of AMPK pathway.