University Presentation Showcase: Undergraduate Division

Project Title

Cellular uptake and targeting of Pt-Mal-LHRH toward metastatic ovarian cancer cells

Presenter Hometown

Wilder, KY

Major

Biomedical Sciences

Department

Biological Sciences

Degree

Undergraduate

Mentor

Lindsay E. Calderon

Mentor Department

Biological Sciences

Abstract

Every year in the United States an estimated 22,000 women will receive an ovarian cancer diagnosis and 14,000 women will succumb to the disease. Due to the nature of the disease, ovarian cancer is difficult to detect in its early stages limiting treatment options. Our recent work is focused on the development of a novel chemotherapeutic agent that will target ovarian cancer cells while also reducing deleterious side effects.

Previous studies have shown an overexpression of the luteinizing hormone-releasing hormone (LHRH) receptor on A2780 and A2780-cis cells. We have designed and synthesized a selective chemotherapeutic agent, Pt-Mal-LHRH, to target this receptor. Platinum is used in common chemotherapeutic agents such as cisplatin and carboplatin, which elicit detrimental side effects without targeting ovarian cancers. Further, cisplatin has high rate of resistance formation in patients.

To address whether Pt-Mal-LHRH is more selective than carboplatin and cisplatin, drug uptake and MTT assays were conducted. The uptake assay screened for platinum concentrations within the cells to indicate the amount of our chemotherapeutic drug capable of entering the cells. In both cell lines, data suggests significance between Pt-Mal-LHRH and carboplatin. Uptake results also showed a significant cisplatin resistance in the A2780-cis line. The MTT assay compared cytotoxicity at different concentrations and its data shows significance between Pt-Mal-LHRH and carboplatin at 100µM in A2780 cells. In A2780-cis cells, the data showed a significance at 1µM concentration between cisplatin and both Pt-Mal-LHRH and carboplatin suggesting cisplatin resistance in the cell line.

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Cellular uptake and targeting of Pt-Mal-LHRH toward metastatic ovarian cancer cells

Every year in the United States an estimated 22,000 women will receive an ovarian cancer diagnosis and 14,000 women will succumb to the disease. Due to the nature of the disease, ovarian cancer is difficult to detect in its early stages limiting treatment options. Our recent work is focused on the development of a novel chemotherapeutic agent that will target ovarian cancer cells while also reducing deleterious side effects.

Previous studies have shown an overexpression of the luteinizing hormone-releasing hormone (LHRH) receptor on A2780 and A2780-cis cells. We have designed and synthesized a selective chemotherapeutic agent, Pt-Mal-LHRH, to target this receptor. Platinum is used in common chemotherapeutic agents such as cisplatin and carboplatin, which elicit detrimental side effects without targeting ovarian cancers. Further, cisplatin has high rate of resistance formation in patients.

To address whether Pt-Mal-LHRH is more selective than carboplatin and cisplatin, drug uptake and MTT assays were conducted. The uptake assay screened for platinum concentrations within the cells to indicate the amount of our chemotherapeutic drug capable of entering the cells. In both cell lines, data suggests significance between Pt-Mal-LHRH and carboplatin. Uptake results also showed a significant cisplatin resistance in the A2780-cis line. The MTT assay compared cytotoxicity at different concentrations and its data shows significance between Pt-Mal-LHRH and carboplatin at 100µM in A2780 cells. In A2780-cis cells, the data showed a significance at 1µM concentration between cisplatin and both Pt-Mal-LHRH and carboplatin suggesting cisplatin resistance in the cell line.