抑制自噬可提高胰腺癌细胞对碳离子放疗的敏感性

IF 2.5 Q3 CELL BIOLOGY
Makoto Sudo, Hiroko Tsutsui, Shuhei Hayashi, Koubun Yasuda, Keiko Mitani, Nana Iwami, Makoto Anzai, Toshiro Tsubouchi, Mitsuaki Ishida, Sohei Satoi, Tatsuaki Kanai, Seiko Hirono, Etsuro Hatano, Jiro Fujimoto
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引用次数: 0

摘要

背景/目的:胰腺癌是所有癌症类型中生存率最低的。因此,开发一种有效的治疗策略对这种癌症至关重要。方法:对人胰腺癌细胞系进行碳离子放射治疗(CIRT),分析其存活、凋亡、坏死和自噬情况。为了研究CIRT诱导的自噬的作用,在CIRT之前向细胞中添加自噬抑制剂。为了评估肿瘤的形成,我们将cirt处理过的小鼠胰腺癌细胞接种在同基因小鼠的腹部,并测量肿瘤的重量。我们用免疫组织化学方法测量了接受新辅助化疗(NAC)加CIRT或单独接受NAC的胰腺癌患者手术切片中的自噬水平。结果:CIRT降低胰腺癌细胞的存活率,诱导凋亡和坏死改变,并伴有自噬。用自噬抑制剂预孵育加速细胞死亡。接种对照胰腺癌细胞的小鼠出现肿瘤,而接种CIRT/自噬抑制剂处理的细胞的小鼠出现明显的逃避。NAC治疗患者的手术标本表达与对照组相当,而NAC + CIRT组的手术标本表达很少自噬和核染色。结论:CIRT通过抑制胰腺癌细胞的自噬诱导能力有效杀伤胰腺癌细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

Background/aims: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer.

Methods: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone.

Results: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining.

Conclusion: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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