Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck

Paul M. Spring, Susanne M. Arnold, Shahin Shajahan, Brandee Brown, Swatee Dey, Subodh M Lele, Joseph Valentino, Raleigh Jones, Mohammed Mohiuddin, Mansoor M. Ahmed

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Abstract

This study evaluated the combined effect of Low Dose Fractionated Radiation (LDFRT) and Taxotere (TXT) therapy on the growth of SCCHN (squamous cell carcinoma of head and neck; SQ-20B, a p53 mutant SCCHN cell line) tumors in a nude mouse model to exploit the increased hyper radiation sensitivity (HRS) phenomenon present in G2/M cell cycle phase when induced by low doses of radiation that was demonstrated in in vitro settings. Seventy-eight animals were randomized into one control group and 5 treatment groups (treatments were administered weekly for six weeks). Tumor regression was observed in all the groups, however, tumor regression was not significant in 2 Gy or TXT or 2 Gy plus TXT treated groups when compared to control group. The tumor regression was significant in both the LDFRT group (p < 0.0043) and LDFRT + TXT group (p < 0.0006) when compared to the other groups. A significantly prolonged tumor growth delay was observed in LDFRT group (p < 0.0081). Importantly, in combination of TXT and LDFRT, no tumor regrowth was observed in 12 out of 13 mice since LDFRT + TXT treatment caused a sustained regression of tumors for 9 weeks. Molecular analysis of resected tumor specimens demonstrated that Bax levels were elevated with a concomitant increase in cytochrome c release into the cytosol in treatment Group VI. These findings strongly suggest that LDFRT can be used in combination with TXT to potentiate the effects of drug on tumor regression through an apoptotic mode of death. Furthermore, the G2/M cell cycle arrest by TXT appears to be an important component of the enhanced apoptotic effect of TXT + LDFRT combined treatment.

Original languageEnglish (US)
Pages (from-to)479-485
Number of pages7
JournalCell Cycle
Volume3
Issue number4
StatePublished - Jan 1 2004

Fingerprint

docetaxel
Radiation Effects
Heterografts
Nude Mice
Dosimetry
Tumors
Radiation
Neoplasms
Cells
G2 Phase Cell Cycle Checkpoints
Carcinoma, squamous cell of head and neck
Epithelial Cells
Control Groups
Radiation Tolerance
Therapeutics
Growth
Cytochromes c
Tumor Cell Line

Keywords

  • Chemopotentiation
  • Hyper-radiation sensitivity
  • Low dose radiation
  • Taxotere
  • Tumor growth delay
  • Tumor regression
  • Xenografts

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Spring, P. M., Arnold, S. M., Shajahan, S., Brown, B., Dey, S., Lele, S. M., ... Ahmed, M. M. (2004). Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck. Cell Cycle, 3(4), 479-485.

Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck. / Spring, Paul M.; Arnold, Susanne M.; Shajahan, Shahin; Brown, Brandee; Dey, Swatee; Lele, Subodh M; Valentino, Joseph; Jones, Raleigh; Mohiuddin, Mohammed; Ahmed, Mansoor M.

In: Cell Cycle, Vol. 3, No. 4, 01.01.2004, p. 479-485.

Research output: Contribution to journalArticle

Spring, PM, Arnold, SM, Shajahan, S, Brown, B, Dey, S, Lele, SM, Valentino, J, Jones, R, Mohiuddin, M & Ahmed, MM 2004, 'Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck', Cell Cycle, vol. 3, no. 4, pp. 479-485.
Spring, Paul M. ; Arnold, Susanne M. ; Shajahan, Shahin ; Brown, Brandee ; Dey, Swatee ; Lele, Subodh M ; Valentino, Joseph ; Jones, Raleigh ; Mohiuddin, Mohammed ; Ahmed, Mansoor M. / Low dose fractionated radiation potentiates the effects of taxotere in nude mice xenografts of squamous cell carcinoma of head and neck. In: Cell Cycle. 2004 ; Vol. 3, No. 4. pp. 479-485.
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abstract = "This study evaluated the combined effect of Low Dose Fractionated Radiation (LDFRT) and Taxotere (TXT) therapy on the growth of SCCHN (squamous cell carcinoma of head and neck; SQ-20B, a p53 mutant SCCHN cell line) tumors in a nude mouse model to exploit the increased hyper radiation sensitivity (HRS) phenomenon present in G2/M cell cycle phase when induced by low doses of radiation that was demonstrated in in vitro settings. Seventy-eight animals were randomized into one control group and 5 treatment groups (treatments were administered weekly for six weeks). Tumor regression was observed in all the groups, however, tumor regression was not significant in 2 Gy or TXT or 2 Gy plus TXT treated groups when compared to control group. The tumor regression was significant in both the LDFRT group (p < 0.0043) and LDFRT + TXT group (p < 0.0006) when compared to the other groups. A significantly prolonged tumor growth delay was observed in LDFRT group (p < 0.0081). Importantly, in combination of TXT and LDFRT, no tumor regrowth was observed in 12 out of 13 mice since LDFRT + TXT treatment caused a sustained regression of tumors for 9 weeks. Molecular analysis of resected tumor specimens demonstrated that Bax levels were elevated with a concomitant increase in cytochrome c release into the cytosol in treatment Group VI. These findings strongly suggest that LDFRT can be used in combination with TXT to potentiate the effects of drug on tumor regression through an apoptotic mode of death. Furthermore, the G2/M cell cycle arrest by TXT appears to be an important component of the enhanced apoptotic effect of TXT + LDFRT combined treatment.",
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AU - Lele, Subodh M

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