PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to <sup>125</sup>I particle irradiation

Pingping LIU; Chenyu WANG; Yunhua XIAO; Chuang HE; Junru XIONG; Liangyu DENG; Xuequan HUANG

doi:10.16016/j.2097-0927.202311143

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PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation

Basic Medicine | 更新时间：2026-01-09

- PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation
- Journal of Army Medical University Vol. 46, Issue 9, Pages: 1015-1023(2024)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院核医学科
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX1501)
- DOI：10.16016/j.2097-0927.202311143
  CLC： R730.23;R730.55;R735.7
- Received：28 November 2023，
  
  Revised：2024-01-16，
  
  Published：15 May 2024
- 稿件说明：
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Pingping LIU, Chenyu WANG, Yunhua XIAO, et al. PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation[J]. Journal of Army Medical University, 2024, 46(9): 1015-1023.
DOI：

Pingping LIU, Chenyu WANG, Yunhua XIAO, et al. PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation[J]. Journal of Army Medical University, 2024, 46(9): 1015-1023. DOI： 10.16016/j.2097-0927.202311143.

摘要

目的

探究孕激素受体膜组分1(progesterone receptor membrane component 1，PGRMC1)介导的自噬对

125

I粒子照射肝癌细胞辐射敏感性的影响。

方法

肝癌细胞Huh7和LM3分别暴露于不同剂量(0、2、4、6、8 Gy)的

125

I粒子，利用透射电镜观察细胞自噬情况。使用自噬抑制剂氯喹(chloroquine，CQ)、激动剂雷帕霉素(rapam

ycin，Rapa)和PGRMC1抑制剂AG-205验证PGRMC1介导的自噬在肝癌细胞对

125

I粒子照射敏感性中的作用。利用CCK-8、克隆形成实验、流式细胞术检测细胞增殖、集落形成及凋亡情况，Western blot检测细胞中PGRMC1、微管相关蛋白轻链3-Ⅰ(microtubule-associated protein light chain 3-Ⅰ，LC3-Ⅰ)、LC3-Ⅱ和p62相对表达量。

结果

不同剂量

125

I粒子照射后Huh7和LM3细胞增殖和克隆形成能力显著降低(

＜0.05)，细胞凋亡数显著增加(

＜0.01)，且呈剂量依赖性。与0 Gy组相比，6 Gy组Huh7和LM3细胞中LC3-Ⅱ/LC3-Ⅰ比值显著增加(

＜0.01)，p62表达显著下调(

＜0.01)。与6 Gy组相比，6 Gy+CQ组Huh7和LM3细胞增殖能力和克隆形成数显著下降(

＜0.05)，细胞凋亡显著增加(

＜0.05)，而6 Gy+Rapa组上述结果则相反。与6 Gy组相比，6 Gy+AG205组Huh7和LM3细胞LC3-Ⅱ/LC3-Ⅰ比值显著降低(

＜0.05)，p62表达显著上调(

＜0.05)，细胞增殖能力和克隆形成数显著降低(

＜0.01)，细胞凋亡显著增加(

＜0.01)，而6 Gy+PGRMC1组上述结果则相反。

结论

125

I粒子照射诱导的PGRMC1升高可促进细胞自噬，从而增加肝癌细胞的增殖及克隆形成能力，减少肝癌细胞的凋亡。

Abstract

Objective

To investigate the effect of progesterone receptor membrane component 1 (PGRMC1) mediated autophagy on the sensitivity of liver cancer cells to

125

I particles irradiation.

Methods

Hepatoma cell lines Huh7 and LM3 were exposed to different doses (0

6 and 8 Gy) of

125

I particles

and cell autophagy was observed by transmission electron microscopy (TEM). Then

autophagy inhibitor chloroquine (CQ)

agonist rapamycin (Rapa)

and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to

125

I particle irradiation. Cell proliferation

colony formation and apoptosis were detected by CCK-8 assay

clonal formation test and flow cytometry

respectively. The expression levels of PGRMC1

microtubule-associated protein light chain 3-Ⅰ (LC3-Ⅰ)

LC3-Ⅱ and p62 were detected by Western blotting.

Results

Different doses of

125

I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells (

0.05)

and increased the apoptotic cells (

0.01)

in a dose-dependent manner. Compared with the 0 Gy group

the ratio of LC3-Ⅱ/ LC3-Ⅰ in Huh7 and LM3 cells was obviously increased

and the expression of p62 was significantly down-regulated in the 6 Gy group. The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly

and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group

while the above results were on the contrary in the 6 Gy+Rapa group. The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells

up-regulated p62 expression

reduced cell proliferation capacity and clone formation ability

and enhanced cell apoptosis when compared with the 6 Gy group

and the above results of the 6 Gy+PGRMC1 group were opposite.

Conclusion

Increment of PGRMC1 induced by

125

I irradiation can promote autophagy

increase the proliferation and clonogenesis

and reduce the apoptosis in hepatocellular carcinoma cells.

关键词

Keywords

references

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⁰

PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation

DOI：10.16016/j.2097-0927.202311143

摘要

Abstract

关键词

Keywords

references

PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation