We have located links that may give you full text access.
Membrane translocation and activation of GnRH receptor sensitize prostate cancer cells to radiation.
International Journal of Radiation Biology 2021 September 15
BACKGROUND: GnRH analogues are widely used as neoadyuvant agents for radiotherapy in prostate cancer (PCa) patients, with well documented effects in reducing tumor bulk and increasing progression-free survival. GnRH analogs act locally in the prostate by triggering apoptosis of PCa cells via activation of the GnRH receptor (GnRHR). During PCa progression, the distribution of GnRHR within the cell is altered, with reduced expression in the cell membrane and remaining sequestered in the endosplasmic reticulum. Pharmacoperone IN3 is able to relocalize GnRHR to the cell membrane. The aim of this study was to evaluate the effect of radiation on PCa cells pretreated with leuprolide, alone or in combination with IN3, as radiosensitizers. Material and methods: PC3 and human PCa primary cell cultures were treated with IN3 for 24 hours, followed by different doses of leuprolide for 48 hours and, finally, single doses of radiation (3, 6 and 9 Gy). After radiation, cell survival, apoptosis, cell cycle distribution, and colony growth were evaluated. Results: Radiation reduced cell survival and increased apoptosis in a dose dependent manner. This effect was also directly related to leuprolide concentration. Pretreatment with IN3 enhanced apoptosis and decreased cell survival, also observing a higher proportion of cells arrested in G2. Conclusion: Neoadyuvant leuprolide increases radiation-mediated apoptosis of PCa cells. This effect was enhanced by pretreatment with pharmacoperone IN3. Clinical use of IN3 as a radiosensitizer combined with androgen deprivation therapy to improve survival of patients with PCa remains to be evaluated.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app