Heavy ion beams induce survivin expression in human hepatoma SMMC-7721 cells more effectively than X-rays.
High linear energy transfer (LET) heavy ion radiation is more effective in inducing biological damage than low-LET X-rays or gamma-rays. Heavy ion beam provides good dose localization (Bragg peak) in critical cancer tissue and gives higher relative biological effectiveness in cell killing across the dose peak, so high-LET heavy ion beam is superior to low-LET radiation in cancer treatment. Survivin, as a member of the inhibitor of apoptosis protein family, might help cancerous cells to overcome the G2/M apoptotic checkpoint and favor the aberrant progression of transformed cells through mitosis. Survivin expression in the human hepatoma SMMC-7721 cell line after exposure to low-LET X-ray and high-LET carbon ion irradiation was investigated in this study. Compared with X-ray irradiation, the carbon ion beam clearly caused G2/M arrest and promoted the expression of the survivin gene in a dose-dependent manner. Clonogenic survival assay showed that SMMC-7721 cells were more radiosensitive to the high-LET carbon ions than to the X-rays, and the radiosensitivity was promoted after treatment with specific survivin short interfering RNA. Differential survivin expression at both transcriptional and translational levels was found for SMMC-7721 cells following low- and high-LET irradiation. The overexpression of survivin in SMMC-7721 cells is probably an important reason why the cancerous cells have radioresistance to strong stimulus such as dense ionizing high-LET radiation. However, the direct killing effect on cancerous cells by high-LET radiation might be more significant than the apoptosis inhibition through the overexpression of survivin following heavy ion irradiation.
Gong
Li
L
School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Jin
Xiaodong
X
Li
Qiang
Q
Liu
Jiangtao
J
An
Lizhe
L
D017209:Apoptosis / Q000528:radiation effects; D002244:Carbon; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000528:radiation effects; D020450:Heavy Ions; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D018499:Linear Energy Transfer; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008938:Mitosis / Q000528:radiation effects; D011836:Radiation Tolerance; D013997:Time Factors; D014965:X-Rays
D051034:Inhibitor of Apoptosis Proteins; D002244:Carbon