Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells

Seema Gupta, Tulay Koru-Sengul, Susanne M. Arnold, Gayathri R. Devi, Mohammed Mohiuddin, Mansoor M. Ahmed

Research output: Contribution to journalArticle

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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 x 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 D0, 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 (SF2)] 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.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalMolecular Cancer Therapeutics
Volume10
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

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Radiation Tolerance
Radiation Effects
Cisplatin
Lung Neoplasms
Radiation
Apoptosis
Non-Small Cell Lung Carcinoma
Radiation Dosage
Survival
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Cell Cycle
Flow Cytometry
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells. / Gupta, Seema; Koru-Sengul, Tulay; Arnold, Susanne M.; Devi, Gayathri R.; Mohiuddin, Mohammed; Ahmed, Mansoor M.

In: Molecular Cancer Therapeutics, Vol. 10, No. 2, 02.2011, p. 292-302.

Research output: Contribution to journalArticle

Gupta, Seema ; Koru-Sengul, Tulay ; Arnold, Susanne M. ; Devi, Gayathri R. ; Mohiuddin, Mohammed ; Ahmed, Mansoor M. / Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells. In: Molecular Cancer Therapeutics. 2011 ; Vol. 10, No. 2. pp. 292-302.
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