Bortezomib induced autophagy to protect esophageal cancer cells from apoptosis through endoplasmic reticulum stress-mediated way

Bortezomib (BZ), a proteasome inhibitor, is a cancer drug for treatment of multiple myeloma and several solid tumors. Studies about BZ therapy on esophageal cancer (EC) are few. Further investigation is necessary. The present study examined the effects of BZ on EC cells and assessed the underlying molecular mechanisms. BZ was observed to inhibit cell viability while promoting cell apoptosis of EC cells, suggesting the anti-tumor effects of BZ for EC therapy. However, BZ may also induce autophagy through increasing the number of LC3+ puncta, Beclin1 expression, and LC3 II/I ratio dose-dependently in EC cells. Activation of autophagy by Rapamycin (Rapa) treatment upregulated cell viability while suppressing cell apoptosis, compared with the BZ treated group, while inhibition of autophagy by Chloroquine (CQ) treatment had the opposite function. Results indicated that BZ could induce protective autophagy, counteracting the anti-tumor effects of BZ in EC cells. Moreover, inhibition of ER stress enhanced the anti-tumor effects of BZ through inhibiting cell viability while promoting cell apoptosis, compared with the BZ treated group. In summary, present results demonstrate that inhibition of ER stress could enhance the anti-tumor effects of BZ via suppressing protective autophagy in EC cells. Cumulative data indicates that BZ exerted anti-tumor effects and induced protective autophagy through ER stress-mediated way in EC cells. Combination of BZ with autophagy inhibitors or ER stress inhibitors could enhance the anti-tumor effects of BZ for EC therapy.