Enhancement of radiosensitivity of the MCF-7 breast cancer cell line with human chorionic gonadotropin.
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 (0.2-5 IU/ml) for 24 h prior to exposing the cells to 0 Gy, 3 Gy, 4 Gy, or 5 Gy 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 2 IU/ml of hCG for at least 24 h prior to irradiation with 4 Gy. 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 24 h was sufficient to achieve the maximum effect. However, maintaining the cells in hCG beyond 24 h 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 2 Gy, a typical dose used in conventional cancer therapy.
Pond-Tor
Sunthorn
S
Milkhaus Laboratory, Inc, Brown University Medical School, Providence, RI 02912, USA.
Rhodes
Ryan G
RG
Dahlberg
Paul E
PE
Leith
John T
JT
McMichael
John
J
Dahlberg
Albert E
AE
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006063:Chorionic Gonadotropin; D011838:Radiation-Sensitizing Agents