چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| زینب مظلومی | اول |
| حجت اله نوزاد چروده | سوم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Introduction: High metastasis, resistance to common treatments, and high mortality rate, have made triple-negative breast cancer (TNBC) to be the most invasive type of breast cancer. TNBC is an invasive subtype of breast cance (containing 15–20%) that does not express Her-2, Estrogen, and Progesterone receptors. TNBC cells have cancer stem cells’ (CSCs’) origin with less differentiated properties and high proliferation levels. TNBC patients are resistant to conventional therapy and display higher metastasis, disease recurrence, and mortality rates than other subtypes of breast cancer. According to the studies, telomerase activity is high in over 90% of breast cancers. 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. This study has been aimed to evaluate intrinsic-, and extrinsic-apoptosis and DNMT3a and TET2 expression following the inhibition of telomerase and mitochondria respiration in TNBC cell lines. Methods: The TNBC cells were treated with IC50 levels of BIBR1532, tigecycline, and their combination. Then, telomere length, and DNMT3a, TET2, and hTERT expression were evaluated. Finally, apoptosis rate, apoptosis-related proteins, and genes were analyzed. Results: 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. Conclusion: 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 |
| کلمات کلیدی | Cancer stem cell, Telomerase, Mitochondria, DNMT3a, TET2 |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Genomix.GIF | 1404/01/23 | 194375 | دانلود |
| 40330409.png | 1404/01/23 | 3407328 | دانلود |
| CGC2024-Abstract-Book3.pdf | 1404/01/23 | 16374488 | دانلود |
