Abstract
ObjectivesTo compare the biological effects of 125I seeds continuous low-dose-rate (CLDR) radiation and 60Co γ-ray high-dose-rate (HDR) radiation on non-small cell lung cancer (NSCLC) cells.Materials and MethodsA549, H1299 and BEAS-2B cells were exposed to 125I seeds CLDR radiation or 60Co γ-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM). The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay.ResultsAfter irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively) and a higher apoptotic ratio for A549 and H1299 cells than after 60Co γ-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.Conclusions 125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies.
Highlights
Lung cancer is the most common cancer and the leading cause of cancer-related deaths in gender-independent populations, accounting for 14% of all cancers and 28% of all cancer-related deaths worldwide [1, 2]
Western blot assays revealed that 125I seeds continuous low-dose-rate (CLDR) radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation
125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells
Summary
Lung cancer is the most common cancer and the leading cause of cancer-related deaths in gender-independent populations, accounting for 14% of all cancers and 28% of all cancer-related deaths worldwide [1, 2]. Non-small cell lung cancer (NSCLC) accounts for approximately 80–85% of all lung cancer cases, and approximately 40% of these patients are diagnosed with advanced NSCLC or medically inoperable disease with a 5-year overall survival rate of less than 15% [1, 3]. In patients who are diagnosed with advanced NSCLC or medically inoperable disease, radiation therapy is usually an important treatment option; this therapy includes 60Co γ-ray highdose-rate (HDR) radiation and 125I seeds continuous low-dose-rate (CLDR) radiation. 125I seeds CLDR radiation has gradually been used in the local treatment of patients with advanced and inoperable prostate cancer, lung cancer, pancreatic cancer, colorectal cancer and esophageal cancer [5,6,7,8,9].
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