Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (3): 615-622.doi: 10.13481/j.1671-587X.20210310

• Research in basic medicine • Previous Articles     Next Articles

Effect of betulinic acid on proliferation and apoptosis of myeloma cells by regulating JAK2/STAT3 signaling pathway and its mechanism

Jia FENG1,Haichan XU1,Jian WEN2,Zehua WU1,Yi CHEN1()   

  1. 1.Department of Hematology,Shenzhen Hospital,Peking University,Beijing 518035,China
    2.Department of Spinal Surgery,Shenzhen Hospital,Peking University,Beijing 518035,China
  • Received:2020-10-28 Online:2021-05-28 Published:2021-05-28
  • Contact: Yi CHEN E-mail:hongjiahongjia1981@163.com

Abstract: Objective

To investigate the effect of betulinic acid(BA) on the proliferation and apoptosis of the myeloma cells through the Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3) signaling pathway and its mechanism.

Methods

The myeloma U266 cells were treated with different concentrations(0,20,40,60,80,100,120,and 160 μmol·L-1) of BA as different concentrations of BA groups, at the same time,blank group (without BA and without cells) was set up,and the U266 cells without BA treatment were used as control group.The proliferation rates of the U266 cells in various groups were detected. The U266 cells were divided into control group and 20, 40,and 60 μmol·L-1 BA groups. The proliferation rates of the cells in various groups were detected by CCK-8 method;the apoptotic rates of the cells in various groups were detected by Annexin Ⅴ-FITC/PI double staining method; the expression levels of c-myc oncogene(c-Myc),cell cycle proteins D1(cyclin D1),B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein (Bax) and JAK2/STAT3 signaling pathway proteins in the cells in various groups were detected by Western blotting method.The nude mice were divided into control group(given 100 μL DMSO)and 20,30 and 40 mg·kg-1 BA group(given 20,30,40 mg·kg-1 BA);the weights and volumes of tumor of the nude mice in various groups were observed.

Results

Compared with control group, the proliferation rate of the myeloma U266 cells at 48 and 72 h after treatment,the expression levels of C-MYc, cyclin D1, Bcl-2, and JAK2/STAT3 signaling pathway proteins in the cells and the tumor weight of nude mice in 20,40, and 60 μmol·L-1 BA groups were significantly decreased(P<0.05), while the apoptotic rates and the expression levels of Bax protein were significantly increased (P<0.05).Forty-eight and 72 h after treatment,compared with 20 μmol·L-1 BA group,the proliferation rates of the myeloma U266 cells in 40 and 60 μmol·L-1 BA groups, and the expression levels of c-MYc, cyclin D1, Bcl-2,and JAK2/STAT3 signaling pathway proteins in the cells in 40 and 60 μmol·L-1 BA groups were significantly decreased(P<0.05), while the apoptotic rates and the expression levels of Bax protein were significantly increased (P<0.05);compared with 40 μmol·L-1 BA group, the proliferation rates of the cells in 60 μmol·L-1 BA group,the expression levels of c-MYc, cyclin D1, Bcl-2, and JAK2/STAT3 signaling pathway proteins in the cells in 60 μmol·L-1 BA group were significantly decreased(P<0.05), while the apoptotic rates and the expression level of Bax protein were significantly increased (P<0.05).Compared with control group, the tumor weights and volumes of the nude mice in 20, 30,and 40 mg·kg-1 BA groups were significantly decreased (P<0.05). Compared with 20 mg·kg-1 BA group, the tumor weight and volume of the nude mice in 30 and 40 mg·kg-1 BA groups were significantly decreased (P<0.05).Compared with 30 mg·kg-1 BA group, the tumor weight and volume in 40 mg·kg-1 BA group were significantly decreased (P<0.05).

Conclusion

BA can promote the apoptosis of myeloma cells and inhibit the proliferation of myeloma cells and the growth of transplanted tumor in the nude mice. The mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway activation by BA.

Key words: betulinic acid, Janus kinase2/signal transducers and activators of transcription3, myeloma cells, proliferation, apoptosis

CLC Number: 

  • R733.3