Results Radiation suppresses cell viability of breast cancer cells VEGF level was measured by using VEGF ELISA kit. The VEGF content of MCF 7, ZR 75 1, MDA MB 231, MDA MB 468 and T 47D was found to be 297. 91 32. 62, 493. 32 33. 31, 1829. 11 50. 01, 1429. 51 40. 01 and 948. 21 20. 11 ng ml respectively per 106 cells. The VEGF content Wortmannin molecular weight of normal human mammary epithelial cells was 110. 00 11. 12 ng ml, and is signifi cantly lower than the breast cancer cells. To compare the effect of UV B on cell viability of breast cancer cells in vitro, MCF 7, ZR 75 1, MDA MB 468, MDA MB 231 and T 47D, and normal mammary epithelial HMEpC cells were treated with in creasing doses of UV B radiation and incu bated in culture medium for 2 days.

UV B reduced cell viability in a dose dependent manner and the cell growth inhibition Inhibitors,Modulators,Libraries was prominent mainly between UV B doses of 10 100 Inhibitors,Modulators,Libraries J m2. The IC50 values of UV B irradi ated MCF 7, ZR 75 1 MDA MB 468, MDA MB 231, and T 47D cells were 101. 20 3. 86, 74. 21 4. 01, 32. 54 2. 67, 35. 33 1. 23, and 42. 12 2. 12 J m2 respectively, where as IC50 was found to be higher as par as HMEpC was concerned. The VEGF level of MCF 7 is low est among the cell lines but IC50 of UV B in MCF 7 was found to be highest. MDA MB 231 and MDA MB 468 have highest level of VEGF and they were shown to be more radiosensitive to UV B. Moreover the VEGF content of HMEpC is very less and hence showed reduced sensitivity towards UV B mediated cell killing, in dicating the role of UV B phototherapy may be an alterna tive substitute for conventional radiotherapy.

Based on the sensitivity to UV B, we have chosen two cancer cell lines for further experiments Inhibitors,Modulators,Libraries i. e.MCF 7 and MDA MB 468 to study the potentiating effect of UV B influenced by ZD6474. ZD6474 in combination Inhibitors,Modulators,Libraries with UV B cooperatively inhibits growth in vitro To evaluate potential cooperative interactions between dual tyrosine kinase inhibitor ZD6474 and UV B, it was also necessary to study a dose re sponse curve of ZD6474 in breast cancer cells. It was found that ZD6474 executed lesser toxicity in normal HMEpC as compared to breast cancer cells. Thus it is anticipated that combinatorial effect of ZD6474 and UV B will Inhibitors,Modulators,Libraries result in more efficient killing in breast cancer cells with minimal effect in normal breast epithelial cells. As a proof of principal, cells were treated with in creasing doses of UV B followed by treatment with 1 or 5 or 10 uM ZD6474. The effect of dual TKI ZD6474 with UV B showed combinatorial benefit. Treatment with ZD6474 in combination with UV B resulted a leftward shift sellekchem of the dose response curves, indicating a greater cytotoxic effect.