AMPK Expressed By Multiple Myeloma Cells Inhibited Metformin-Induced Myeloma Cells Proliferation

Background

Multiple myeloma(MM) is a malignant plasma cells proliferative disease which is characterized by increased blood calcium level, renal insufficiency, anemia, and bone lesions(CRAB). MM is still uncured disease. To further explore the mechanisms of MM was an urgent problem needs to be solved. AMPK is an "energy sensor". Studies had demonstrated that metformin could activate AMPK and exert anti-tumor effect in many tumors. However, a paradoxical phenomenon was found that knockdown AMPK could enhance the anti-tumor effect of metformin. Recent studies had revealed that AMPK maybe a double-edged sword in tumors. Our previous study had discovered that metformin exert anti-myeloma effect without activating AMPK. In this study, we mainly focus on the expression of AMPK in MM cells and to explore whether the expression of AMPK in MM cells could block the anti-myeloma effect of metformin.

Methods

The expression of AMPK in MM cells was detected by Western blotting. Small interfering RNA(siRNA) was used to knockdown the expression of AMPK. Apoptotic cells of MM cells were detected by Annexin V-FITC/PI using flow cytometry analysis. Western blotting was used to elucidate the apoptotic protein of MM cells induced by metformin with or without knockdown AMPK.

Results

Our study revealed that AMPK was obviously expressed by MM cells(Fig.1). Metformin could not activate AMPK signaling pathway. Knockdown AMPK with siRNA could enhance the anti-myeloma effect of metformin(Fig.2 and Fig.3).

Conclusions

Taken together, our data indicated that AMPK was expressed by MM cells. Inhibit AMPK could enhance the anti-myeloma effect of metformin. AMPK maybe a new therapy target.