Fig. 6.

Autophagy impairs synergistic effects of Sal and anti-tumor agents against CRC. a Although Sal exerts anti-proliferative and pro-apoptotic effects, it triggered autophagy of CRC cells, which counteracts the anti-tumor effects of Sal alone or in combination with anti-tumor agents. b Sal up-regulated p-AMPK, but down-regulated p-mTOR, p-NF-κB (p65), TGF-β, p-JAK2 and p-STAT3 in CRC cells. It was demonstrated that autophagy induced by Sal mainly associates with AMPK activation. Blockage of AMPK signaling via compound C and AMPK knockdown or direct inhibition of autophagy via 3-MA increased effectiveness of combined use of Sal with anti-tumor agents against CRC, which suggests that autophagy impairs synergistic effects of Sal and anti-tumor agents