Abstract
BackgroundRadiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 μM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells.MethodsDT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western’s blotting assay.ResultsThe results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells.ConclusionsDT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.
Highlights
IntroductionDespite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur
Radiotherapy plays an important role in the treatment of prostate cancer
dihydroisotanshinone I (DT) and the combination treatment can block cell motility in different human prostate cancer cells To study the effect of DT on the migration ability of prostate cancer cells, we used two prostate cancer cell lines (PC-3 and DU145) to study the function of DT, IR, and the combined therapy with 5 μM DT and 5 Gy IR in the migration assay (Fig. 1b, c)
Summary
Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Radiotherapy is an effective form of local cancer treatment because it induces the DNA damage response (DDR) [1]. Sensors inside cells can recognize DNA damage and start the DDR process, which induces cell cycle arrest to allow the. Lee et al BMC Pharmacology and Toxicology (2018) 19:5 phase can be delayed. These DDR proteins can be crucial in cancer treatment with chemotherapy agents and radiotherapy. Despite the sophisticated radiation techniques that have been developed, as well as the combination of radiation with chemotherapy, some tumors do recur. A method that improves the local control of primary or metastasized tumors with a combination of radiotherapy and radiosensitizer may be beneficial for patients with cancer
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