Understanding the role of T-type VGCC and ER-β in triple-negative breast cancer

Sahu, Chittaranjan and Bhargava, A. (2020) Understanding the role of T-type VGCC and ER-β in triple-negative breast cancer. Masters thesis, Indian institute of technology Hyderabad.

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Abstract

Triple-Negative Breast Cancer (TNBC) doesn’t express Estrogen Receptor-α (ER-α), Progesterone Receptor (PR), and Human Epidermal Growth Receptor (HER 2). Out of the total breast cancers reported, 15-20% are of TNBC type. Out of the overall mortality caused in breast cancer, 50% of the death is caused due to TNBC alone. Due to the absence of these growth receptors, the TNBC cannot be treated using traditional therapies targeting these growth receptors. Therefore it is important to identify new receptors and channels that can be targeted to treat the TNBC. TNBC cells expresses the ER-β receptor, but the role of the ER-β receptor was not clear in the earlier published papers. So it is essential to understand the role of ER-β in TNBC so that it can be used as a target for future therapy. In earlier published results, the role of the T-type VGCC in proliferation was evident.So,the ER-β receptor and T-type VGCC can be used as a target for the future therapy of TNBC. MDA MB 231 cells(Model for the TNBC) were treated with either ER-β Agonist (DPN) or T-type VGCC blocker (NNC) or a combination DPN, and NNC and the results (proliferation and proliferation migration) were compared with untreated sample. MDA MB 231 cells treated with ER-β activator DPN at 150 nM manifested a decrease in proliferation but had no impact on the migration. The above observation shows that ER-β plays a prominent role in proliferation of cells but not in migration of cells. MDA MB 231 cells treated with T-type VGCC blocker NNC at 5.6 μM and above showed a decrease in as well as migration, suggesting the role of T type VGCC in proliferation and migration. A combination of NNC 5.6 μM and DPN 150 nM manifested a significant reduction in rate of proliferation and migration relative to the untreated sample. The decrease in proliferation and migration due to the combination of drugs(NNC 5.6 μM and DPN 150 nM) is more than the addition of the decrease in proliferation and migration due to the individual treatment with NNC 5.6 μM and DPN 150 nM. From this result, we can conclude that a synergistic effect is observed due to the combination of NNC 5.6 μM and DPN 150 nM. So the combination of NNC 5.6 μM and DPN 150 nM can be used as a future therapeutics for the TNBC.

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