Procyanidin C1 combined with olaparib induces senescence in BRCA1-proficient breast cancer cells.

IF 3.1 3区医学 Q2 ONCOLOGY

American journal of cancer research Pub Date : 2026-08-15 eCollection Date: 2026-01-01 DOI:10.62347/LYCQ1366

Chengsi Ren, Chengshi Fu, Xingtong Chen, Renfei Yang, Jinyong He, Anran Gao, Qunshan Su, Xiangyun Teng, Jianhua Xu

引用次数: 0

Abstract

PARP inhibitors (PARPi) are effective only in BRCA1-mutated tumors, with BRCA1-proficient patients deriving minimal benefit. Here, we demonstrate that PCC1 persistently induces double-strand DNA breaks (DSBs) in BRCA1-proficient breast cancer cells. Critically, PARP inhibition blocks base excision repair (BER), leading to accumulation of DNA damage and direct activation of senescence programs. Compared to monotherapy, the combination of olaparib and PCC1 significantly enhanced cellular senescence and suppressed tumor growth. In sum, we developed a novel therapeutic regimen that extends the utility of PARP inhibitors to BRCA1-proficient breast cancer patients through synergistic co-targeting of DNA damage responses.

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原花青素C1联合奥拉帕尼可诱导brca1精通的乳腺癌细胞衰老。

PARP抑制剂（PARPi）仅对brca1突变的肿瘤有效，精通brca1的患者获益甚微。在这里，我们证明了PCC1在brca1精通的乳腺癌细胞中持续诱导双链DNA断裂（DSBs）。关键的是，PARP抑制阻断了碱基切除修复（BER），导致DNA损伤的积累和衰老程序的直接激活。与单药治疗相比，奥拉帕尼与PCC1联合治疗可显著增强细胞衰老，抑制肿瘤生长。总之，我们开发了一种新的治疗方案，通过协同靶向DNA损伤反应，将PARP抑制剂的应用范围扩展到brca1精通的乳腺癌患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American journal of cancer research ONCOLOGY-

自引率

3.80%

发文量

263

期刊介绍： The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.