SIRT1 and cancer: In contrast, the knockdown of Sirt1 with Sirt1-ASO in multicellular-TME resulted in the elimination of the blocking effect of resveratrol on the expression of the mentioned biomarkers, indicating the superior targeting of resveratrol (Figure 7) and the leading role of Sirt1 in resveratrol-promoting anti-cancer activity in CRC cells even in multicellular-TME.