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Biochemistry Commons

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Theses/Dissertations

Virginia Commonwealth University

Sildenafil

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Full-Text Articles in Biochemistry

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu Jan 2019

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically achievable enterohepatic …


Celecoxib Enhances Sorafenib/Sildenafil Lethality In Cancer Cells And Reverts Platinum Chemotherapy Resistance, Timothy A. Webb Jan 2016

Celecoxib Enhances Sorafenib/Sildenafil Lethality In Cancer Cells And Reverts Platinum Chemotherapy Resistance, Timothy A. Webb

Theses and Dissertations

The present studies sought to determine whether the lethality of the drug combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also, in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1 and ABCG2. Over-expression of GRP78 and HSP27 maintained pump expression in the presence of drugs. Cell killing …