TAT-RasGAP317–326 Enhances Radiosensitivity of Human Carcinoma Cell Lines In Vitro and In Vivo through Promotion of Delayed Mitotic Cell Death
Pelagia G. TsoutsouAlessandro AnnibaldiDavid ViertlJonathan OllivierFranz BucheggerMarie‐Catherine VozeninJean BourhisChristian WidmannOscar Matzinger
12
Citation
29
Reference
10
Related Paper
Citation Trend
Abstract:
The synthetic peptide TAT-RasGAP317–326 has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP317–326 when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP317–326, clonogenic assays were performed using four human cancer cell lines, HCT116 p53 / (ATCC: CCL-247), HCT116 p53–/–, PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493). Next, to investigate tumor growth delay after irradiation, HCT116 cell lines were selected and xenografted onto nude mice that were then treated with TAT-RasGAP317–326 alone or in combination with radiation or cisplatin. Afterwards, cell cycle and death modulation were investigated by quantification of micronuclei and apoptosis-related protein array. TAT-RasGAP317–326 radiosensitized all four human carcinoma cell lines tested but displayed no effect on normal cells. It also displayed no effect when administered as monotherapy. This radiosensitizing effect was confirmed in vivo in both p53-positive and p53-negative HCT116 xenografts. TAT-RasGAP317–326 combined with radiation enhanced the number of cells in S phase and subsequently delayed cell death, but had almost no effect on major apoptosis-related proteins. TAT-RasGAP317–326 is a radiosensitizing agent that acts on carcinoma cells and its radiosensitizing effect might be mediated, at least in part, by the enhancement of mitotic cell death.Keywords:
Radiosensitivity
Human cell
Carcinoma Cell
Hepatic carcinoma
Human cell
Carcinoma Cell
Cite
Citations (0)
Radiosensitivity
Human cell
Cite
Citations (0)
Human cell
Carcinoma Cell
Cite
Citations (0)
Human cell
Carcinoma Cell
Cite
Citations (0)
Radiosensitivity
Human cell
Radiation Tolerance
Radiobiology
Cite
Citations (2)
There are many pathways to cell death during normal physiological and pathological processes, including necrosis, apoptosis, mitotic cell death, autophagy and so on. Mitotic cell death is a delayed reproductive death characterised by an aberrant form of mitosis associated with the formation of multinucleate giant cell that are temporarily viable but reproductively dead. We do not yet understand what mechanism triggers mitotic cell death, and how it is linked to other cell death routes.
Mitotic catastrophe
Multinucleate
Cite
Citations (2)
目的 探讨人肾上腺皮质癌SW-13细胞株的培养方法及生物学特性.方法 将SW-13细胞株进行体外培养,MTT法检测其生长曲线,电镜下、光镜下进行细胞形态学观察.结果 细胞需在37℃,无CO2,偏碱性环境下培养,6～8h完全贴壁,2d左右进入对数生长期.细胞生物学性状稳定.结论 SW-13细胞株是一种生物学特性稳定、实用的细胞株,相信随着研究的进一步深入,其必将发挥更大的作用价值,有着更广的研究领域。
Carcinoma Cell
Human cell
Cite
Citations (0)
Carcinoma Cell
Human cell
Cite
Citations (0)
The Relationship of DNA Double-strand Break Induction to Radiosensitivity in Human Tumour Cell Lines
SummaryRecent data suggest that the differences in radiosensitivity between cell lines can be related to differences in dsb induction (Radford 1986a). In the light of this we have set out to assess the extent to which differences in radiation survival between human tumour cell lines can be attributed to differences in dsb induction. For nine human tumour lines survival was assayed by clonogenic assay and compared with dsb induction by irradiation at ice-bath temperature as measured by neutral filter elution. The lines varied widely in their sensitivity, ranging from a sensitive neuroblastoma (surviving fraction at 2 Gy, SF2 = 0·13) to a resistant bladder carcinoma (SF2 = 0·62). Dsb induction was found to vary between the cell lines, such that resistant cells generally suffered less damage than sensitive ones. However, the relationship between damage induction and celluar sensitivity was not a simple one, and other factors which may influence sensitivity need to be invoked. These data suggest that, in human tumour cell lines, differences in radiosensitivity may at least in part be due to different levels of damage induction, but that some lines may vary in their tolerance of damage due to differences in biological characteristics such as repair capacity.
Radiosensitivity
Human cell
Radiobiology
Cite
Citations (75)
Radiosensitivity
Double strand
Human cell
Radiation Tolerance
Cite
Citations (64)