丁酸钠联合电离辐射对肺癌A549细胞凋亡的影响及其机制

doi:10.13481/j.1671-587X.20220410

Abstract

Abstract: Objective

To explore the effects of histone deacetylase inhibitor （HDACi） sodium butyrate （NABT） alone or combined with X-ray irradiation on the apoptosis of human non-small cell lung cancer A549 cells， and to clarify its mechanism.

Methods

The A549 cells in logarithmic growth phase were divided into control group， NaBt group， 4 Gy X-ray irradiation group and NaBt combined with 4 Gy X-ray irradiation group. Flow cytometry was used to detect the apoptotic rates at 24 and 48 h after treatment. After 6 h of irradiation， the mitochondrial membrane potential （Δψm） and ROS （reative oxygen species） levels in the cells of various groups were analyzed by flow cytometry. After 24 h of irradiation， the expression levels of caspase-3 and p21 mRNA in the cells in various groups were detected by real-time quantitative PCR （RT-qPCR）.

Results

After 4 Gy irriadiation for 24 and 48 h， compared with control group， 4 Gy X-ray irradiation group and NaBt group， the apoptotic rate of cells in NaBt combined with 4 Gy X-ray irradiation group was significantly increased （P<0.05 or P<0.01）. Compared with control group， the apoptotic rate of cells in NaBt group was significantly increased after 48 h of irradiation （P<0.01）. After treated with NaBt alone or combined with 4 Gy X-ray for 6 h， compared with control group， 4 Gy X-ray irradiation and NaBt group， the Δψm of A549 cells in NaBt combined with 4 Gy X-ray irradition group was decreased （P<0.05）. Compared with control group， the ROS levels in NaBt group and NaBt combined with 4 Gy X-ray irradiation group were increased （P<0.05）. Compared with 4 Gy X-ray irradiation group， the ROS level in NaBt combined with 4 Gy X-ray irradiation group was increased （P<0.05）. After treated with NaBt alone or combined with 4 Gy X-ray irradiation for 24 h， the mRNA levels of caspase-3 and p21 in the cells in NaBt combined with 4 Gy X-ray irradiation group were significantly higher than those in control group， 4 Gy X-ray irriadiation group and NaBt group （P<0.01）. Compared with control group， the p21 mRNA levels in NaBt group and 4 Gy X-ray irriadiation group were significantly increased （P<0.01）.

Conclusion

NaBt can induce the apoptosis of A549 cells， and its mechanisms may be related to the regulation of mitochondrial apoptosis pathway.

Key words: Histone deacetylase inhibitor, Sodium Butyrate, Non-small cell lung cancer, Apoptosis, Mitochondrial membrane potential

CLC Number:

R734.2

Qingxu LANG,Xueshuang NIU,Kaiwen YANG,Ren ZHANG,Siteng WANG, ZUMIRETIGULI·Wumaier,Zhenqi WANG. Effects of sodium butyrate combined with ionizing radiation on apoptosis of lung cancer A549 cells and its mechanism[J].Journal of Jilin University(Medicine Edition), 2022, 48(4): 915-921.

Figures/Tables 5

Fig. 1

Tab. 1

Fig. 2

Tab. 2

Tab. 3

References 24

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Group	Apoptotic rate
Group	（t/h） 24	48
Control	11.51±4.59	14.33±1.57
NaBt	25.92±1.92	79.08±2.56^**
4 Gy X-ray irradiation	10.99±4.33	20.71±7.21
NaBt combined with 4 Gy X-ray irradiation	43.60±5.86^*^△△^＃	89.29±0.36^**^△^＃＃

Group	Δψm	ROS
Control	14.15±3.85	2.23±0.90
NaBt	6.79±0.51	13.87±4.64^*
4 Gy X-ray irradiation	6.94±1.38	2.65±0.57
NaBt combined with 4 Gy X-ray irradiation	2.81±0.79^*^△^＃	16.84±3.06^*＃

Group	Caspase-3	P21
Control	1.00±0.18	1.00±0.16
NaBt	1.32±0.10	6.85±0.30^*＃＃
4 Gy X-ray irradiation	0.92±0.19	3.68±0.19^*
NaBt combined with 4 Gy X-ray irradiation	2.75±0.53^*^△^＃	16.09±1.67^*^△△^＃＃

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Effects of sodium butyrate combined with ionizing radiation on apoptosis of lung cancer A549 cells and its mechanism

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