6-姜辣素对人多发性骨髓瘤细胞的抑制作用及分子机制

doi:10.3969/j.issn.1006-5725.2024.23.003

Abstract

Abstract:

Objective To investigate the inhibitory effect and elucidate the molecular mechanism of 6?gingerol on human multiple myeloma cells. Methods The human multiple myeloma cell lines RPMI 8226 and ARH77 were cultured in vitro， followed by treatment with varying concentrations （50， 100， 200， 300， 400 μmol/L） of 6?gingerol. The inhibitory effect on cell proliferation was assessed using the CCK?8 assay. Flow cytometry was employed to evaluate cell apoptosis and cycle distribution. Additionally， qRT?PCR and Western blotting techniques were utilized to analyze gene and protein expression levels. Results The proliferation of RPMI 8226 and ARH77 cells was dose? and time?dependently inhibited by 6?gingerol， leading to the induction of apoptosis with statistically significant differences （P < 0.05）. Further mechanistic investigations revealed that treatment with 6?gingerol arrested RPMI 8226 cells in the G0/G1 phase， resulting in a significant increase in Bax levels and a decrease in Bcl?2 mRNA and c?Myc mRNA levels （P < 0.05）. Additionally， it significantly upregulated the expression of Bax， Cleaved?PARP， Cleaved?caspase3， P53， and p?AKT proteins while down regulating the expression of Bcl?2 protein （P < 0.05）. Conclusions The compound 6?Gingerol exhibits inhibitory effects on the proliferation and induction of apoptosis in MM cells， as well as cell cycle arrest at the G0/G1 phase. Its mechanism of action is likely associated with the suppression of the AKT signaling pathway， downregulation of Bcl?2 family protein expression， and inhibition of c?Myc expression.

Key words: multiple myeloma, 6-gingerol, cell proliferation, cell apoptosis, signal pathway

CLC Number:

R559

Chunfang KONG,Anna LI,Bo KE,Weirong DING,Tingting LIU,Huan FU,Tingting ZHANG,Chenghao JIN,Mei. WU. The inhibitory effect and molecular mechanism of 6-gingerol on human multiple myeloma cells[J]. The Journal of Practical Medicine, 2024, 40(23): 3291-3297.

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References 31

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时间	DMSO	50 μmol/L	100 μmol/L	200 μmol/L	300 μmol/L	400 μmol/L	F值	P值
24 h	0.00 ± 0.00	3.05 ± 0.87^*	5.18 ± 0.42^**	9.88 ± 0.49^**	16.19 ± 0.72^**	27.73 ± 0.72^**	951.30	< 0.001
48 h	0.00 ± 0.00	3.88 ± 0.75^**	8.15 ± 0.28^**	17.72 ± 0.68^**	27.68 ± 0.63^**	44.94 ± 2.71^**	587.63	< 0.001
72 h	0.00 ± 0.00	8.31 ± 1.16^**	13.29 ± 1.12^**	25.54 ± 1.31^**	36.32 ± 1.15^**	60.48 ± 1.01^**	1298.38	< 0.001

时间	DMSO	50 μmol/L	100 μmol/L	200 μmol/L	300 μmol/L	400 μmol/L	F值	P值
24 h	0.00 ± 0.00	3.32 ± 0.62^*	7.77 ± 0.51^***	14.43 ± 1.21^**	27.36 ± 0.62^**	35.91 ± 0.60^**	1 463.74	< 0.001
48 h	0.00 ± 0.00	4.93 ± 0.42^*	10.53 ± 0.41^***	21.45 ± 1.62^***	39.14 ± 0.69^***	61.42 ± 1.85^***	1 438.98	< 0.001
72 h	0.00 ± 0.00	9.12 ± 0.78^***	17.58 ± 0.88^***	31.05 ± 1.29^***	48.53 ± 1.42^***	76.19 ± 0.93^***	1 409.23	< 0.001

项目	DMSO	50 μmol/L	100 μmol/L	200 μmol/L	300 μmol/L	400 μmol/L	F值	P值
ARH77	2.60 ± 0.41	7.86 ± 1.47^**	10.20 ± 1.00^**	12.71 ± 1.17^***	19.47 ± 1.79^***	39.23 ± 3.12^***	171.48	< 0.001
RPMI?8226	3.66 ± 0.44	7.92 ± 0.67^*	11.09 ± 0.84^**	16.99 ± 1.20^***	31.69 ± 1.22^***	56.56 ± 0.85^***	1420.24	< 0.001

细胞周期	DMSO	300 μmol/L	400 μmol/L	F值	P值
G₁期	16.90 ± 0.86	30.95 ± 1.06^***	40.31 ± 1.90^****	228.41	< 0.001
S期	64.11 ± 0.60	61.44 ± 5.88	48.82 ± 0.46^***	17.08	0.003
G₂期	18.96 ± 0.96	7.61 ± 4.81^*	10.88 ± 2.35^**	10.78	0.011

项目	DMSO	300 μmol/L	400 μmol/L	F值	P值
Bcl-2	1	0.744 ± 0.055^*	0.108 ± 0.012^****	591.68	< 0.001
C-myc	1	0.817 ± 0.079^*	0.714 ± 0.079^**	75.20	0.004
Bax	1	1.260 ± 0.101^*	3.427 ± 0.485^***	65.02	< 0.001

The inhibitory effect and molecular mechanism of 6-gingerol on human multiple myeloma cells

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项目	DMSO	300 μmol/L	400 μmol/L	F值	P值
Bcl-2	1	0.813 ± 0.102^*	0.627 ± 0.171^*	7.92	0.021
Bax	1	1402 ± 0.114^**	1.669 ± 0.149^**	28.93	0.001
Cleaved-PARP	1	1.781 ± 0.200^**	2.380 ± 0.490^**	15.41	0.004
Cleaved-caspase3	1	1.764 ± 0.188^**	1.9113 ± 0.114^***	44.77	< 0.001
P53	1	1.809 ± 0.261^**	2.124 ± 0.376^**	14.47	0.005

项目	DMSO	300 μmol/L	400 μmol/L	F值	P值
P-AKT	1	0.702 ± 0.007^*	0.593 ± 0.026^**	70.69	< 0.001
AKT	1	0.962 ± 0.096	0.882 ± 0.245	0.47	0.648
P-ERK	1	0.745 ± 0.226	0.864 ± 0.124	4.34	0.068
ERK	1	1.041 ± 0.097	1.066 ± 0.172	0.25	0.784
P-STAT3	1	1.261 ± 0.228	0.996 ± 0.196	2.30	0.181
STAT3	1	0.976 ± 0.114	0.883 ± 0.104	1.44	0.309

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