title: Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells.
abstract: In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non-small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 × 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D(0), the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF(2))] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin + 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non-small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition.
authors.affiliation: Department of Radiation Oncology, University of Miami, 1475 NW 12th Ave (D-31), Miami, FL 33136, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Gupta
authors.forename: Tulay
authors.initials: T
authors.lastname: Koru-Sengul
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Arnold
authors.forename: Gayathri R
authors.initials: GR
authors.lastname: Devi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Ahmed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D011836:Radiation Tolerance / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin