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一项关于端粒酶激活剂调节A375皮肤癌细胞系增殖功效的初步研究。

A pilot study on the efficacy of a telomerase activator in regulating the proliferation of A375 skin cancer cell line.

作者信息

Makalakshmi M K, Banerjee Antara, Pathak Surajit, Paul Sujay, Sharma Neeta Raj, Anandan B

机构信息

Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, India.

Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, 603103, India.

出版信息

Mol Biol Rep. 2024 Dec 20;52(1):69. doi: 10.1007/s11033-024-10161-z.

Abstract

INTRODUCTION

The changes in histone modifications are linked to the progression of benign and normal tissue to malignancy. Thus, numerous findings suggest that targeting epigenetic factors might be a focus for anti-cancer treatment. In this study, we tested the hypothesis that telomerase activator might be a potential epigenetic regulator in combatting skin cancer cell proliferation.

METHODS

Melanoma cell line A375 cells were treated with telomerase activator TA-65. Cell senescence assay was done to evaluate the senescence induction. Morphological changes and differences in expression of HDACs and hTERT genes were studied. Further, hyaluronidase and anti-oxidant assays were also performed. Additionally, telomerase enzyme and 20S proteasome activity was also studied.

RESULTS

Morphological changes were observed in treated cells and it is evident that telomerase activator induced cellular senescence in high concentrations. From our results, it is evident that HDAC8 and  HDAC10 expression was upregulated, whereas hTERT gene expression was downregulated in treated groups. This suggests that the telomerase activator has a regulatory role in skin cancer cells proliferation by targeting the epigenetic factors.

CONCLUSION

Targeting HDACs and hTERT in the treatment of melanoma is a prominent concern. In our current study, we highlight the most recent research, although in its initial stage, involving various epigenetic factors involved in melanoma cells proliferation.

摘要

引言

组蛋白修饰的变化与良性和正常组织向恶性肿瘤的进展有关。因此,大量研究结果表明,靶向表观遗传因子可能是抗癌治疗的一个重点。在本研究中,我们检验了端粒酶激活剂可能是对抗皮肤癌细胞增殖的潜在表观遗传调节剂这一假设。

方法

用端粒酶激活剂TA-65处理黑色素瘤细胞系A375细胞。进行细胞衰老检测以评估衰老诱导情况。研究形态学变化以及HDACs和hTERT基因表达的差异。此外,还进行了透明质酸酶和抗氧化检测。另外,还研究了端粒酶和20S蛋白酶体活性。

结果

在处理后的细胞中观察到形态学变化,很明显端粒酶激活剂在高浓度下诱导细胞衰老。从我们的结果来看,很明显在处理组中HDAC8和HDAC10的表达上调,而hTERT基因表达下调。这表明端粒酶激活剂通过靶向表观遗传因子在皮肤癌细胞增殖中具有调节作用。

结论

在黑色素瘤治疗中靶向HDACs和hTERT是一个突出的关注点。在我们目前的研究中,我们强调了尽管尚处于初始阶段,但涉及黑色素瘤细胞增殖中各种表观遗传因子的最新研究。

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