The Effect Of A Small Molecule Inhibitor In Combination With Eve On Growth Of Cancer Cells

Erin Scott

School Name

Governor's School for Science and Math

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Dr. Sakuntala Warshamana-Greene; Department of Biological and Physical Sciences, South Carolina State University

Abstract

The IGF-1/IGF-1R pathway is an intracellular signally pathway involved with cancer. Deactivation of this pathway leads to decreased cell proliferation. The pathway is typically inhibited at a key protein kinase in the pathway, the mammalian target of rapamycin (mTOR), using everolimus (EVE). A negative feedback loop involving the IGF-1/IGF1R pathway has been shown to bypass this inhibition. We sought to determine whether deactivating the pathway at two points was more effective than deactivating it at only one. We treated cells with AEW, a small molecule inhibitor of IGF-1R, and EVE. Alone, neither of the two drugs significantly decreased cell growth. In combination, they did significantly decrease cell growth. We found evidence of apoptosis in cells treated with the drugs individually and in combination based on levels of caspase, cleaved caspase, PARP, and cleaved PARP measured using a Western Blot, but that the apoptotic markers did not correspond to the decrease in cell growth. EVE and AEW used in combination more effectively decrease cell growth than when used singly, but this increased effectiveness cannot be explained by apoptosis alone.

Location

Owens 201

Start Date

4-16-2016 11:45 AM

COinS
 
Apr 16th, 11:45 AM

The Effect Of A Small Molecule Inhibitor In Combination With Eve On Growth Of Cancer Cells

Owens 201

The IGF-1/IGF-1R pathway is an intracellular signally pathway involved with cancer. Deactivation of this pathway leads to decreased cell proliferation. The pathway is typically inhibited at a key protein kinase in the pathway, the mammalian target of rapamycin (mTOR), using everolimus (EVE). A negative feedback loop involving the IGF-1/IGF1R pathway has been shown to bypass this inhibition. We sought to determine whether deactivating the pathway at two points was more effective than deactivating it at only one. We treated cells with AEW, a small molecule inhibitor of IGF-1R, and EVE. Alone, neither of the two drugs significantly decreased cell growth. In combination, they did significantly decrease cell growth. We found evidence of apoptosis in cells treated with the drugs individually and in combination based on levels of caspase, cleaved caspase, PARP, and cleaved PARP measured using a Western Blot, but that the apoptotic markers did not correspond to the decrease in cell growth. EVE and AEW used in combination more effectively decrease cell growth than when used singly, but this increased effectiveness cannot be explained by apoptosis alone.