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源自人类组成性表达蛋白LPTS/PinX1的端粒酶活性抑制剂TPCH的广谱抗肿瘤分析

Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1.

作者信息

Zhou Hongchang, Zhang Xiaoying, Wang Yao, Wu Yongqiang, Wang Ling, Hu Chen, Zhang Ting, Zhang Hui, You Dian, Zhao Mengli, Zhao Mujun, Li Anqi, Chen Guangming

机构信息

Huzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, China.

Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Huzhou University, Huzhou, China.

出版信息

Front Oncol. 2025 Aug 15;15:1643155. doi: 10.3389/fonc.2025.1643155. eCollection 2025.

DOI:10.3389/fonc.2025.1643155
PMID:40896430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12394036/
Abstract

BACKGROUND

The human liver-related putative tumor suppressor LPTS/PinX1 is a gene encoding a telomerase inhibitory protein. Overexpression of LPTS/PinX1 protein can inhibit the growth of multiple telomerase-positive cancer cell lines. LPTS/PinX1 has therapeutic potential for cancer.

METHODS

We statistically analyzed the level of LPTS/PinX1 protein in 9 cancer cell lines. LPTS/PinX1158-328 (exon 7 of LPTS) was fused with TAT to generate the recombinant protein TPCH. The effects of the TPCH protein on cell growth, senescence and apoptosis in 14 cell lines were analyzed and .

RESULTS

The purified TPCH protein was delivered into cells and inhibited telomerase activity. Also it inhibited the growth of 11 telomerase-positive cancer cell lines, was ineffective in 3 telomerase-negative cell lines and inhibited the growth of MCF-7, A549 and SW480 cell line-derived xenograft (CDX) and liver cancer patient-derived xenograft (PDX) mouse models The inhibitory effect on the cancer cell growth was negatively correlated with the telomere length. The TPCH protein induced senescence and apoptosis in telomerase-positive cancer cells through the p21 signaling pathway and inhibited the migration of telomerase-positive cancer cells.

CONCLUSIONS

The TPCH protein strongly inhibited telomerase activity and suppressed the growth of all tested human telomerase-positive cancer cell lines and . Therefore, it could be developed as a broad-spectrum anticancer agent with low toxicity.

摘要

背景

人类肝脏相关的假定肿瘤抑制因子LPTS/PinX1是一个编码端粒酶抑制蛋白的基因。LPTS/PinX1蛋白的过表达可抑制多种端粒酶阳性癌细胞系的生长。LPTS/PinX1在癌症治疗方面具有潜力。

方法

我们对9种癌细胞系中LPTS/PinX1蛋白的水平进行了统计学分析。将LPTS/PinX1158 - 328（LPTS的第7外显子）与TAT融合以产生重组蛋白TPCH。分析了TPCH蛋白对14种细胞系的细胞生长、衰老和凋亡的影响。

结果

纯化后的TPCH蛋白被递送至细胞内并抑制端粒酶活性。它还抑制了11种端粒酶阳性癌细胞系的生长，对3种端粒酶阴性细胞系无效，并抑制了MCF - 7、A549和SW480细胞系来源的异种移植瘤（CDX）以及肝癌患者来源的异种移植瘤（PDX）小鼠模型的生长。对癌细胞生长的抑制作用与端粒长度呈负相关。TPCH蛋白通过p21信号通路诱导端粒酶阳性癌细胞衰老和凋亡，并抑制端粒酶阳性癌细胞的迁移。

结论

TPCH蛋白强烈抑制端粒酶活性，并抑制所有测试的人类端粒酶阳性癌细胞系的生长。因此，它可被开发为一种低毒的广谱抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/e23d7df8aa25/fonc-15-1643155-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/830676a60984/fonc-15-1643155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/13843ea9ef6d/fonc-15-1643155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/93117e6dfb44/fonc-15-1643155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/2073e49f663b/fonc-15-1643155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/bc000fc5e0d8/fonc-15-1643155-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/e23d7df8aa25/fonc-15-1643155-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/830676a60984/fonc-15-1643155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/13843ea9ef6d/fonc-15-1643155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/93117e6dfb44/fonc-15-1643155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/2073e49f663b/fonc-15-1643155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/bc000fc5e0d8/fonc-15-1643155-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/12394036/e23d7df8aa25/fonc-15-1643155-g006.jpg

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