The activation of AMPK by treating AICAR in BR colon cancer cells restored the inhibitory effect on cell proliferation through the inhibition of Akt/mTOR signaling and reduced the induction of autophagy, indicating that the activation of AMPK reduces resistance to butyrate and restores the sensitivity of butyrate relative to inhibitory effects on cell proliferation; thus, AMPK may play an important role in the regulation of resistance to butyrate by Akt/mTOR activation under stressful conditions. Here, MTOR is linked to colonic neoplasm.