The Effects Of Fractionated Ionizing Radiation On The Multidrug Resistance In Tumor Cells

The multidrug resistance in tumor cells is the main obstacle in the cancer treatment in clinical recently. The tumor cells can resist to either chemotherapy or radiotherapy. According to analysis by American cancer society, the deathes in cancer patients are associated with primary MDR in 61% and acquired MDR in 33% annually. Therefore, it is most meaningful to reverse MDR in cancer treatment clinically. Recently, the mechanisms of MDR have been investigated deeply by researchers, and the mainly ones will be discussed as follows: (1) Drug efflux pump membrane glycoprotein mediated MDR such as P-gp; (2) Enzyme mediated MDR such as optimize (TOPO), glutathione S-transferase (GST), protein kinase C (PKC) and so forth; (3) Anti-apoptosis genes mediated MDR such as bcl-2 family, p53, C-myc and so on; (4) Cell adhesion molecular mediated MDR such as integrin; (5) New proteins associated with MDR such as calcium binding protein-Annexins, chaperones- HSP27 and so forth. Recently the relationship between ionizing radiation and MDR is complex, because ionizing radiation can either reverse MDR, or enhance it. Therefore, it is an interesting question to explore the effects of ionizing radiation on MDR in tumor cells, and to optimize ionizing radiation treatment protocols to cure MDR successfully will be an area where radiotherapy and chemotherapy kill the MDR cancer cells together. This study mainly wants to detect the effects of different fractionated ionizing radiation protocols on tumor cells and its'MDR cells with MTT, and try to find the most fine treatment protocols to reverse MDR in tumor cells.1 The detection and contrast of sensitivities between SKOV3 and SKVCR 2.0 cells to different chemical drugsThis study mainly detects the sensitivities of SKOV3 and SKVCR 2.0 cells to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) by using MTT. The result is that resistant cells, SKVCR 2.0 cells, present characteristics of multidrug resistance.2 The first plan: Regular fractionated ionizing radiation (2Gy/time, 1time/d), Total dose 5Gy.This study mainly detects the sensitivities between regular fractionated ionizing radiation group (2Gy/d, 5Gy), single ionizing radiation (5Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKOV3 and SKVCR 2.0 cells by using MTT. The results of experiment suggest that regular fractionated ionizing radiation (2Gy/d, 5Gy) can induce SKOV3 cells to resist higher concentrations of vincristine (VCR).3 The second plan: Regular fractionated ionizing radiation (2Gy/time, 1time/d), Total dose 10Gy.This study mainly detects the sensitivities between regular fractionated ionizing radiation group (2Gy/d, 10Gy), single ionizing radiation (10Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKOV3 and SKVCR 2.0 cells by using MTT. The results of experiment suggest that regular fractionated ionizing radiation (2Gy/d, 10Gy) decreases the resistance of SKVCR 2.0 to higher concentration of cisplatin (CCD) and etoposide (VP-16). Meanwhile, regular fractionated ionizing radiation (2Gy/d, 10Gy) and single ionizing radiation (10Gy) increases the resistance of SKOV3 and SKVCR 2.0 to higher concentration of vincristine (VCR).4 The third plan: Regular fractionated ionizing radiation (2Gy/time, 1time/d), Total dose 15Gy.This study mainly detects the sensitivities between regular fractionated ionizing radiation group (2Gy/d, 10Gy), single ionizing radiation (10Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKVCR 2.0 cells by using MTT. The results of experiment suggest that regular fractionated ionizing radiation (2Gy/d, 15Gy) increases the resistance of SKVCR 2.0 to vincristine (VCR), however it has no effect on the sensitivity of SKVCR 2.0 to cisplatin (CCD) and etoposide (VP-16). 5 The forth plan: Super fractionated ionizing radiation (1Gy/time, 2time/d, interval 4h), Total dose 5Gy.This study mainly detects the sensitivities between hyperfractionated ionizing radiation group (5Gy, 1Gy×2/d, interval 4h), single ionizing radiation (5Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKOV3 and SKVCR 2.0 cells by using MTT. The results of experiment suggest that hyperfractionated ionizing radiation (5Gy, 1Gy×2/d, interval 4h) has no effort on the resistance of SKOV3 and SKVCR 2.0 cells to any concentration of vincristine (VCR). Meanwhile, hyperfractionated ionizing radiation (5Gy, 1Gy×2/d, interval 4h) increases the sensitivity of SKOV3 to few concentrations of cisplatin (CCD) and etoposide (VP-16), and increases the resistance of SKVCR 2.0 to most of concentrations of etoposide (VP-16).6 The fifth plan: Super fractionated ionizing radiation (1Gy/time, 2time/d, interval 4h), Total dose 10Gy.This study mainly detects the sensitivities between hyperfractionated ionizing radiation group (10Gy, 1Gy×2/d, interval 4h), single ionizing radiation (10Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKOV3 and SKVCR 2.0 cells by using MTT. The results of experiment suggest that hyperfractionated ionizing radiation (10Gy, 1Gy×2/d, interval 4h) has no effort on the resistance of SKOV3 and SKVCR 2.0 cells to any concentration of vincristine (VCR), cisplatin (CCD) and etoposide (VP-16).7 The sixth plan: Super fractionated ionizing radiation (1Gy/time, 2time/d, interval 4h), Total dose 15Gy.This study mainly detects the sensitivities between hyperfractionated ionizing radiation group (15Gy, 1Gy×2/d, interval 4h), single ionizing radiation (15Gy), and control to vincristine (VCR), cisplatin (CCD), etoposide (VP-16) in SKOV3 and SKVCR 2.0 cells by using MTT. The results of experiment suggest that hyperfractionated ionizing radiation (15Gy, 1Gy×2/d, interval 4h) has no effort on the resistance of SKOV3 and SKVCR 2.0 cells to most concentration of vincristine (VCR), cisplatin (CCD) and etoposide (VP-16).Therefore, this study mainly contrasted and analyzed the sensitivities of SKOV3 and SKVCR 2.0 cells to vincristine (VCR), cisplatin (CCD) and etoposide (VP-16) directly, and further evaluated the change of their resistances. These results revealed that regular fractionated ionizing radiation group (2Gy/time, 1time/d) reversed the acquired multidrug resistance of SKVCR 2.0 cells to cisplatin (CCD) and etoposide (VP-16), and decreased SKOV3'sensitivities to higher concentrations of vincristine (VCR) and cisplatin (CCD), in either 5Gy or 10Gy total doses. Hyperfractionated ionizing radiation (1Gy×2/d, interval 4h) didn't induce the resistance of SKOV3 to any concentration of vincristine (VCR), cisplatin (CCD) and etoposide (VP-16). These results of this study can provide the basis to the clinical radiotherapy on ovarian cancer, especially on those which represent characteristics of MDR. Meanwhile, this study may make for the further study on the reverse effects of fractionated ionizing radiation on MDR.