Albumin Paclitaxel Compared with 5-Penfluorouracil, Lobaplatin, and Albumin Paclitaxel Combined with 5-Penfluorouracil in the Treatment of Human Gastric Cancer Cell AGS Line Autophagy and Apoptosis.

IF 2.7 4区 医学 Q2 Medicine Canadian Journal of Gastroenterology and Hepatology Pub Date : 2022-06-10 eCollection Date: 2022-01-01 DOI:10.1155/2022/6015877
Xingzhen Cheng, Fang Yang, Yang Wang, Wei Nie, Adarsha Mahendra Upadhyay, Maolin Zhang, Qian Wang, Zhiqiang Yan
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引用次数: 1

Abstract

Background: Gastric cancer is one of the most common malignant tumors in the world. Albumin paclitaxel (Nab-PTX) is a novel microtubule inhibitor with albumin as the carrier. Several clinical trials are underway in gastric cancer, but the autophagy mechanism of Nab-PTX on gastric cancer is still unclear. The autophagy and apoptosis effects of Nab-PTX compared with 5-pentafluorouracil (5-Fu) and lobaplatin (LBP) in gastric cancer are also unclear.

Objective: This article will compare the effects of Nab-PTX, 5-Fu, LBP, and albumin paclitaxel + 5-pentafluorouracil (Nab-PTX + 5-Fu) on AGS cells from the perspective of autophagy and apoptosis, which is to provide new ideas and experimental evidence for gastric cancer.

Method: (1) Experimental groups were control (Ctrl), Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu. (2) CCK-8 assay was used to reflect cell viability and proliferation. (3) The flow cytometry was used to perform the 24-hour apoptosis and cell cycle of each group. (4) Western blot assay was used to investigate autophagy signal proteins LC3I/LC3II, LC3II/LC3I, SQSTM1/p62, Beclin-1, Atg12, Atg5, p-mULK1, p-AMPK, p-mTOR, and apoptosis signal proteins Bax and Bcl-2.

Results: Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu inhibited AGS cells' proliferation and arrested the cell cycle. At the same time, each group increased the apoptosis of AGS cells to various degrees (Nab-PTX + 5-Fu > Nab-PTX > 5-Fu > LBP, respectively). The experimental results showed that Nab-PTX and Nab-PTX + 5-Fu promoted autophagy and apoptosis of AGS cells. The comparison of Nab-PTX, 5-Fu, and LBP between groups revealed that 5-Fu inhibited autophagy and the expression of apoptosis protein Bax. In LBP, abnormal activation of autophagy downstream, blocking of autophagy flow, abnormal increase of ATG12, and increased expression of apoptosis protein Bax occurred. Further study found that the autophagy upstream mechanism is different.

Conclusion: Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu can inhibit cell proliferation, promote cell apoptosis, and induce the difference in autophagy expression. The autophagy difference of this antitumor drug may be related to its inducing apoptosis. Meanwhile, Nab-PTX has a better antitumor effect than 5-Fu and LBP in gastric cancer, and the combination of Nab-PTX + 5-Fu has more antitumor advantages.

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白蛋白紫杉醇与5-潘氟尿嘧啶、洛铂及白蛋白紫杉醇联合5-潘氟尿嘧啶治疗人胃癌AGS细胞自噬和凋亡的比较
背景:胃癌是世界上最常见的恶性肿瘤之一。白蛋白紫杉醇(Nab-PTX)是一种以白蛋白为载体的新型微管抑制剂。一些胃癌的临床试验正在进行中,但Nab-PTX对胃癌的自噬机制尚不清楚。与5-五氟尿嘧啶(5-Fu)和洛铂(LBP)相比,Nab-PTX在胃癌中的自噬和凋亡作用也尚不清楚。目的:本文将从自噬和凋亡的角度比较Nab-PTX、5-Fu、LBP和白蛋白紫杉醇+ 5-五氟尿嘧啶(Nab-PTX + 5-Fu)对胃癌细胞的影响,为胃癌治疗提供新的思路和实验依据。方法:(1)实验组为对照组(Ctrl)、Nab-PTX、5-Fu、LBP、Nab-PTX + 5-Fu。(2) CCK-8法反映细胞活力和增殖情况。(3)流式细胞术检测各组细胞24小时凋亡及细胞周期。(4) Western blot检测细胞自噬信号蛋白LC3I/LC3II、LC3II/LC3I、SQSTM1/p62、Beclin-1、Atg12、Atg5、p-mULK1、p-AMPK、p-mTOR、凋亡信号蛋白Bax、Bcl-2。结果:Nab-PTX、5-Fu、LBP和Nab-PTX + 5-Fu均能抑制AGS细胞的增殖,阻滞细胞周期。同时,各组均不同程度增加AGS细胞凋亡(分别为Nab-PTX + 5-Fu > Nab-PTX > 5-Fu > LBP)。实验结果显示,Nab-PTX和Nab-PTX + 5-Fu促进AGS细胞自噬和凋亡。各组间Nab-PTX、5-Fu和LBP的比较发现,5-Fu抑制细胞自噬和凋亡蛋白Bax的表达。在LBP中,自噬下游异常激活,自噬流动受阻,ATG12异常升高,凋亡蛋白Bax表达增加。进一步研究发现自噬上游机制不同。结论:Nab-PTX、5-Fu、LBP及Nab-PTX + 5-Fu均能抑制细胞增殖,促进细胞凋亡,诱导细胞自噬表达差异。这种抗肿瘤药物的自噬差异可能与其诱导细胞凋亡有关。同时,Nab-PTX在胃癌中的抗肿瘤作用优于5-Fu和LBP,且Nab-PTX + 5-Fu联合使用具有更强的抗肿瘤优势。
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来源期刊
CiteScore
4.80
自引率
0.00%
发文量
0
审稿时长
37 weeks
期刊介绍: Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.
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