Bound Volume Number

Volume III

Document Type

Honors Capstone Project

Capstone Advisor

Thomas Fondy

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Keywords

Low frequency ultrasound, mTOR, Rapamycin, Everolimus, Temsirolimus, Human Leukemia

Capstone Prize Winner

no

Won Capstone Funding

no

Honors Categories

Sciences and Engineering

Subject Categories

Biotechnology

Abstract

It has been shown that the mammalian target of rapamycin (mTOR) pathway, which regulates cell growth and proliferation, is aberrant in many hematological malignancies. Rapamycin inhibits mTOR signaling which regulates cell growth and cell cycle progression. This study sought to determine the effects of mTOR inhibitors on the cell sizes of normal and neoplastic cells and to determine ultrasonic sensitivity of normal and neoplastic cells treated with mTOR inhibitors. The effects of rapamycin (rapa), an extensively studied natural product that affects cell cycle entry by inhibiting mTORC1, and its analogs temsirolimus (tems) and everolimus (eve), were examined on leukemic cell lines (U937: Human monocytic leukemia, THP-1: Human acute monocytic lymphoma, K562: Human chronic myelogenous leukemia, and MOLT-4, Human acute lymphoblastic leukemia) in combination with 20kHz ultrasound. Each cell line was treated for 48 hours with each analog before being exposed to ultrasound. By using low frequency ultrasound of 5 pulses (0.6 seconds of ultrasound and 0.4 seconds without ultrasound) at 20 kHz and 30% amplitude (60W), we determined that as the concentrations of Rapa, Eve, and Tems (2, 20, and 50nM) increased, there is usually the most sonic damage observed in U937, MOLT-4, K562, and THP-1 cells. The most preferentially damaged cell line is K562 by all of the analogs and with all the concentrations used. In addition, larger cells were more susceptible to ultrasonic damage than were smaller cells. Further, there are no significant differences among the three analogs in the potentiation of ultrasonic damage. This preliminary therapeutic approach involving the use of ultra-sound in combination with mTOR inhibitors might eventually provide an improved approach to the treatment of leukemia and other hematological malignancies in a clinical setting.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Biotechnology Commons

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