■高转移,对普通治疗的抵抗力,和高死亡率,使三阴性乳腺癌(TNBC)成为最具侵袭性的乳腺癌类型。高端粒酶活性和线粒体生物发生参与乳腺癌的发生。端粒酶的催化亚基,端粒酶逆转录酶(hTERT),在端粒延长和基因表达等生物学外功能中起作用,线粒体功能,和凋亡。在这项研究中,它的目的是评估内在的-,在TNBC细胞系中抑制端粒酶和线粒体呼吸后,外源性凋亡以及DNMT3a和TET2的表达。
■TNBC细胞用IC50水平的BIBR1532,替加环素,还有他们的组合。然后,端粒长度,和DNMT3a,评估TET2和hTERT表达。最后,凋亡率,凋亡相关蛋白,并对基因进行了分析。
■目前的结果表明,端粒酶的IC50水平和线粒体呼吸的抑制诱导了细胞凋亡,但对端粒长度没有任何显着影响。结果还表明,端粒酶抑制在MDA-MB-231细胞中诱导外源性凋亡,并在MDA-MB-468细胞中引起内源性凋亡。此外,发现p53的表达降低,对细胞凋亡无效。细胞中DNMT3a和TET2的表达增加。此外,联合治疗优于BIBR1532和替加环素单独治疗。
■端粒酶和线粒体呼吸的抑制可引起体内和外凋亡,并增加DNMT3a和TET2的表达,可用于乳腺癌的治疗。
UNASSIGNED: High metastasis, resistance to common treatments, and high mortality rate, has made triple-negative breast cancer (TNBC) to be the most invasive type of breast cancer. High telomerase activity and mitochondrial biogenesis are involved in breast cancer tumorigenesis. The catalytic subunit of telomerase, telomerase reverse transcriptase (hTERT), plays a role in telomere lengthening and extra-biological functions such as gene expression, mitochondria function, and apoptosis. In this study, it has been aimed to evaluate intrinsic-, extrinsic-apoptosis and DNMT3a and TET2 expression following the inhibition of telomerase and mitochondria respiration in TNBC cell lines.
UNASSIGNED: TNBC cells were treated with IC50 levels of BIBR1532, tigecycline, and also their combination. Then, telomere length, and DNMT3a, TET2, and hTERT expression were evaluated. Finally, apoptosis rate, apoptosis-related proteins, and genes were analyzed.
UNASSIGNED: The present results showed that IC50 level of telomerase and inhibition of mitochondria respiration induced apoptosis but did not leave any significant effect on telomere length. The results also indicated that telomerase inhibition induced extrinsic-apoptosis in MDA-MB-231 and caused intrinsic- apoptosis in MDA-MB-468 cells. Furthermore, it was found that the expression of p53 decreased and was ineffective in cell apoptosis. The expressions of DNMT3a and TET2 increased in cells. In addition, combination treatment was better than BIBR1532 and tigecycline alone.
UNASSIGNED: The inhibition of telomerase and mitochondria respiration caused intrinsic- and extrinsic- apoptosis and increased DNMT3a and TET2 expression and it could be utilized in breast cancer treatment.