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Enhancement of radiosensitivity of the MCF-7 breast cancer cell line with human chorionic gonadotropin
Authors:Pond-Tor Sunthorn  Rhodes Ryan G  Dahlberg Paul E  Leith John T  McMichael John  Dahlberg Albert E
Affiliation:(1) Milkhaus Laboratory, Inc., 70 Elm St, Providence, RI 02903, USA;(2) Department of Radiation Oncology, USA;(3) Department of Molecular and Cell Biology & Biochemistry, Brown University Medical School, Providence, RI 02912, USA
Abstract:Secretion of human chorionic gonadotropin (hCG) during pregnancy induces differentiation of the mammary gland, thereby making breast tissue less susceptible to carcinogenesis. HCG binds to specific hCG receptors on mammary epithelial cells inducing changes in gene expression that can inhibit cell proliferation and, therefore, interfere with tumorigenesis. Since breast cancer cells also contain a relatively high level of the hCG receptor, hCG has potential as a therapeutic agent. We postulated that hCG might also enhance the radiosensitivity of breast cancer cells and, therefore, be useful as an adjunctive therapy. In the present study, MCF-7 breast cancer cells grown in cell culture were treated with hCG (0.2–5thinspIU/ml) for 24thinsph prior to exposing the cells to 0 Gy, 3thinspGy, 4thinspGy, or 5thinspGy of radiation. Following irradiation, the MCF-7 cells were incubated either in the presence or absence of hCG. Cell survival was monitored with an MTT assay 1 day, 4 days, and 7 days after irradiation. All of the concentrations of hCG tested enhanced radiosensitivity of MCF-7 cells. The maximum enhancement occurred with MCF-7 cells that had been exposed to 2thinspIU/ml of hCG for at least 24thinsph prior to irradiation with 4thinspGy. The use of higher concentrations of hCG or a higher dose of radiation did not increase the enhancement effect. Treatment of MCF-7 cells with hCG for only 24thinsph was sufficient to achieve the maximum effect. However, maintaining the cells in hCG beyond 24thinsph increased the effectiveness of the lowest hCG concentration. Using a linear-quadratic equation to analyze the data, we determined that the use of hCG would result in an 8–10% reduction in MCF-7 cell survival at a dose of 2thinspGy, a typical dose used in conventional cancer therapy.
Keywords:breast cancer  chorionic gonadotropin  MCF-7  MTT  radiosensitivity
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