[Growth inhibition effect of matrine on K562 cells mediated by IL-6/JAK/STAT3 signaling pathway].

Abstract

OBJECTIVE:

To investigate the molecular mechanism of the growth inhibitory effect of matrine on K562 cells in JAK/STAT3 mediated signal pathway.

METHODS:

Western blot analyses were performed to investigate the differential expression of JAK2, STAT3, phosphor-STAT3 (Tyr705 & Ser727) and phosphor-JAK2 proteins after matrine treatment in K562 cells with or without human recombinant interleukin 6 (IL-6) pretreatment. The expression of STAT3 response gene products such as Bcl-xL, Cyclin D1 and c-Myc, were investigated by Western blot and quantitative real time RT-PCR (qRT-PCR). Expression of IL-6, a potent upstream activating factor of JAK/STAT3 pathway, was analyzed by both real time qRT-PCR and ELISA.

RESUTLS:

Western blot revealed that matrine treatment resulted in a strong down-regulation of phosphor-STAT3 both in Tyr705 and Ser727 sites or phosphor-JAK2 proteins expression without significant effects on the total STAT3 and JAK2 proteins. The expression of phosphor-Tyr705 STAT3 and phosphor-Ser727 STAT3 was decreased to 0.370 ± 0.172 in K562 cells treated with 0.5 mg/ml matrine for 48 h, respectively, from 0.690 ± 0.119 and 1.150 ± 0.263 in control cells, accompanied with a dramatical down-regulation of phosphor-JAK2 from 0.670 ± 0.137 to 0.049 ± 0.057 (P<0.05). In addition, it was found that the expression of Bcl-xL, Cyclin D1, c-Myc was decreased both at the transcription and protein level in K562 cells after matrine treatment. Matrine treatment resulted in a significant decrease in the expression level of IL-6 in K562 cells from (35.1 ± 1.93) to (10.74 ± 1.83) and (8.66 ± 1.24) pg/ml at the dose of 0.5 and 0.8 mg/ml, respectively (p<0.05). Matrine treatment could diminish the up-regulation of STAT3, JAK2, phosphor-STAT3 and phosphor-JAK2 protein following pretreatment with IL-6 in K562 cells.

CONCLUSION:

Matrine exerts its anti-leukemia effect by interfering with the JAK2/STAT3 signaling pathway. The inhibition of IL-6 expression may play a pivotal role in the disruption of JAK/STAT pathway by matrine.

• Authors: Lingdi Ma, Zhichao Zhu, Xiao Sun, Lijia Jiang, Yu Bai, Xuzhang Lu, Min Zhou, Sixuan Qian, Jianyong Li
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 36 Issue 5 Pg. 422-6 (May 2015) ISSN: 0253-2727 [Print] China
• PMID: 26031532 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• IL6 protein, human
• Interleukin-6
• Quinolizines
• STAT3 Transcription Factor
• STAT3 protein, human
• JAK2 protein, human
• Janus Kinase 2
• Matrines

Topics

• Alkaloids
• Down-Regulation
• Humans
• Interleukin-6
• Janus Kinase 2
• K562 Cells
• Quinolizines
• STAT3 Transcription Factor
• Signal Transduction
• Up-Regulation
• Matrines