EXPLORING A COMBINATION USING CHEMOTHERAPY AND TOLFENAMIC ACID TO INDUCE ANTI-PROLIFERATIVE RESPONSE IN MEDULLOBLASTOMA CELL LINES

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dc.creatorChen, Lilingen_US
dc.creatorSankpal, Umeshen_US
dc.creatorBasha, Riyazen_US
dc.creator.orcid0009-0006-0191-1887 (Chen, Liling)
dc.date.accessioned2024-04-16T18:48:04Z
dc.date.available2024-04-16T18:48:04Z
dc.date.issued2024-03-21en_US
dc.description.abstractBackground: Medulloblastoma (MB) is the most common malignant brain tumor in children, with a peak incidence between the ages of 5-9 years old. Originating in the cerebellum, it often metastasizes throughout the CNS via the CSF, making it very difficult to treat. Current treatment options are limited, and includes surgical resection followed by radiation and chemotherapeutic agents. However, these agents are associated with numerous toxicities and long-term neurocognitive deficits in survivors. Our laboratory is interested in identifying drug resistance cell markers and combination therapies that target them to help increase efficacy of the chemotherapeutic agents. We have previously demonstrated that combination therapy of chemotherapeutic agents with Tolfenamic acid (TA), decreased the number of viable cancer cells when compared to the chemotherapeutic agents alone. TA is a non-steroidal anti-inflammatory drug, and its anti-cancer activity can be attributed to its ability to downregulate Specificity Protein 1 (Sp1), a transcription factor responsible for the upregulation of the anti-apoptotic protein, Survivin. Numerous cancerous tumors have been known to express high levels of Sp1 and SurvivIn, however these markers have not been well established in MB. Purpose: The aim of the project is to elucidate the association of Survivin expression in MB cells with the likelihood of patient survival and to test combination treatments of chemotherapeutic agents with the potential Survivin inhibitor, TA. The goal is to reduce the effective dosage of the chemotherapeutic agent Cisplatin, thereby reducing their side effect profiles. Methods: A R2 genomics visualization platform was accessed to obtain data regarding patient survival rates and Survivin expression in MB cells. A Kaplan-Meier curve was then generated to analyze the relationship. MB cell lines, DAOY, and D283 cells were obtained through the ATCC and cultured following standard cell culture conditions. Cells were then treated with vehicle (DMSO) or optimized doses of a chemotherapeutic agents (Vincristine or Cisplatin) with TA. Cell viability was measured at 24h and 48h post-treatment using Cell-TiterGlo kit (Promega) following manufacturer’s instructions. Results: The Kaplan-Meier curve showed that the overexpression of Survivin resulted in a poor prognosis and low survival rates among MB patients. Compared to results of MB cell inhibition with individual agents (Vincristine and Cisplatin) from our previous studies, the combination of TA and Vincristine or TA and Cisplatin showed decreased MB cell growth and downregulation of Survivin. Differential effects of Vincristine and Cisplatin were noted against DAOY and D283 cell lines. Conclusion: These preliminary observations suggest that Survivin expression may be associated with poor prognosis in MB patients and that inhibiting Survivin with TA is inducing the anti-proliferative effects of chemotherapeutic agents in MB cells. Further research involving other chemotherapies is required to understand TA’s role in Survivin inhibition. Understanding the specific effect of Cisplatin can help to design the therapies based on the molecular sub-group of MB.en_US
dc.description.sponsorshipPartially funded by a grant from the Cancer Prevention and Research Institute of Texasen_US
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32605
dc.language.isoen
dc.titleEXPLORING A COMBINATION USING CHEMOTHERAPY AND TOLFENAMIC ACID TO INDUCE ANTI-PROLIFERATIVE RESPONSE IN MEDULLOBLASTOMA CELL LINESen_US
dc.typeposteren_US
dc.type.materialtexten_US

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