Mechanism Of Signal Transduction Of Differential Changes Between Human Lung Epithelial Cells And Lung Cancer Cells Induced By Low-dose Radiation

Malignant tumors are common and frequently-occurring diseasethat threaten human life and health. The chemotherapy and radiotherapyas traditional method of malignancy therapies, cause injury of the normalcells meanwhile killing tumor cells, leading to dysfunction of nervoussystem, hematopoietic system, immune system, reproductive system,digestive system and so on, thereby their clinical application is restricted.Low-dose radiation (LDR) may avoid the injuring effects on the normaltissues, and it enhances immune system function, inhibits tumor growthand metastasis, therefore, LDR displays a broad applied prospect inanti-tumor therapy.Since the last century low-dose radiation was formally put forward,it has been widely known with research for many years. At present, themost studies on it have been done from exploring the phenomenonentering gradually into uncovering the cellular and molecular regulatorymechanisms, evaluation of effects on human health, and exploring itsclinical application. Hormesis is one of the most important biologicaleffects of low-dose radiation. The performance of hormesis showsstimulating the growth of animals and plants, improving fertility,reducing the tumor incidence, activating lymphocytes and enhancingimmune function, etc. At the cellular level, it mainly embodies inaccelerating the proliferation and enhancing immune activity of normalcells. Cellular signal pathways play an important role in biological effectsexerted by cells. Abnormality of some signal pathways may be related tothe biological effects induced by low-dose radiation. Both MAPK/ERKand PI3K/Akt signal pathways are important cellular signal pathways,they exert regulative and control role in the essential physiologicalprocesses, such as cell proliferation, differentiation, survival andapoptosis, etc. However, effects of low-dose radiation on MAPK/ERKand PI3K/Akt signal pathways, the difference of the effects in the normalcells and tumor cells, and the exact clinical significance of the effects anddifference have not been fully clarified.A number of studies show that low-dose radiation has anti-tumoreffect on the whole level in vivo, but the effect on tumor cells may beobscured by immune function of the organism. Therefore, in the presentstudy, cultured human lung epithelial cells and lung cancer cells in vitrowere used for object of the study, the possible mechanism of low-doseradiation-induced biological effects was explored at the cellular level. Inthis study,75mGy was served as observed irradiation dose, Western blotwas used to evaluate the changes of MAPK/ERK and PI3K/AKT signalpathways in human lung epithelial cells and lung cancer cells, and thedifferential signal changes in two kinds of cells after low-dose radiationand after blocked signal pathways with signal blockers were contrastivelyobserved.The main results in the present study are as follows:(1)Low-dose radiation elevated significantly expression level ofphosphorylated-ERK (p-ERK) in human lung epithelial cells andexpression level of ERK in the cells was not changed, indicating thatMAPK/ERK signal pathway was involved hormesis induced by low-dose radiation.(2)Low-dose radiation increased markedly expression level ofp-Akt and expression level of Akt was not affected in human lungepithelial cells, suggeting that PI3K/Akt signal pathway participated inlow-dose radiation-induced hormesis.(3)In human lung cancer cells A549, low-dose radiation did notelevated p-ERK expression, indicating that low-dose radiation failed toactivate MAPK/ERK signal pathway and induce hormesis.(4)In human lung cancer cells A549, low-dose radiation did notupregulate expression of p-Akt protein, showing that low-dose radiationdid not activate PI3K/Akt signal pathway and induce hormesis.These results revealed that low-dose radiation induced hormesis inhuman lung epithelial cells, however, it failed to induce hormesis inhuman lung cancer cells. These differential changes induced by low-doseradiation between human normal cells and lung cancer cells were relatedto low-dose radiation-induced activation of MAPK/ERK and PI3K/Aktsignal pathways.