[Transcription factor EB related autophagy in the treatment of multiple myeloma and its mechanism].

Abstract

Objective: To clarify the effects of bortezomib combined with or without siramesine on the proliferation of multiple myeloma cell lines, the expression changes of transcription factor EBC (TFEB) nuclear translocation and the level of autophagy, and to provide basis for further exploring the regulation mechanism of transcription factor TFEB on autophagy. Methods: The multiple myeloma cell lines RPMI8226 and U266 were cultured in vitro, and the multiple myeloma cells were treated with a certain concentration of bortezomib and siramesine. The changes of cell proliferation inhibition were detected by CCK-8 method. Real time PCR and Western blot were used to detect the relative expression of TFEB, autophagy-related factor LC3B, Beclin1, p62, LAMP1 mRNA and protein. Results: As the concentration of bortezomib increased and the duration of action increased, the proliferation inhibition rates of the two cell lines gradually increased (P<0.05) . The combination of the two drugs has a synergistic inhibitory effect on the proliferation of the above-mentioned multiple myeloma cell lines (P<0.05) . In the blank control group, single drug group, and combination drug group, the relative expression of TFEB mRNA and protein in the cytoplasm decreased sequentially (P<0.05) , and the relative expression of TFEB mRNA and protein in the nucleus increased sequentially (P<0.05) . The relative expression of autophagy-related factors LC3B, Beclin1, LAMP1 mRNA and protein increased sequentially, and the relative expression of p62 mRNA and protein decreased sequentially (P<0.05) . Conclusion: Bortezomib and siramesine can synergistically inhibit the growth of multiple myeloma cells, which is related to the increased autophagy expression in multiple myeloma cell lines and the expression of TFEB with nuclear translocation is also enhanced.