An Effect Of CpG ODN, With X Ray Radiation, On The Radiation Sensitivity Of The Lewis Lung Cancer

Background:As one of the most frequent malignant tumor,most of the lung cancer patients are in the late stage when they visit doctor, radiotherapy is one of the important therapies,but at present,the clinical curative effect is not very satisfactory,local control and metastasis are the major reasons.Moreover,the immunity of many lung cancer patients is weak,and radiotherapy can depress the immune function to influence the radiotherapy sensitivity.Then,for many years,oncology doctors have been paying close attention on founding available radiotherapy sensitizer.Recently,investigators have found that synthetic DNA sequences containing unmethylated cytosine-guanine motifs can activate the immune system,upgrade the immune function, inhibit tumor growth.However,at present,the research and report of CpG ODN with radioactive ray depressing tumor growth is few in our country.Objective:To explore the radiosensitive effect and its possible mechanism of CpG ODN and provide experimental foundation for searching safety and effective radiotherapy sensitizer.Methods:Lewis lung cancer was employed as the model to study the radiosensitive effect of CpG ODN(1826),injected intraperitoneally before radiotherapy,treating mouse Lewis lung cancer.32 C57BL/6J mice were randomly divided into four groups,which containing 8 mice in each group.Group A:the control group,Group B:the X Ray radiation group, Group C:the CpG group;Group D:the CpG with X Ray radiation group. The group A was not dole with at all;The group B was treated with X Ray radiation only,3Gy/Fx,at day 1,3,5,8,10,12,the total dose is 18Gy; The group C was administered with CpG ODN(1826) 0.05mg respectively at day 1,3,5,8,10,12,the total dose is 0.3mg;The group D was administered with CpG ODN(1826) 0.05mg respectively,6 hours before X Ray radiation, the disposalof administration and radiation was the same to group B and C.In the process of experiment,the tumor volume was measured specially with caliper at two days.At the fifth day,we exposed the eyeballs to assemble blood,collected serum and determined the concentration of IL-IO and TNF-α;stripped the tumor architecture,weighed them;and exposed the spleens,calculated the spleen exponent;The apoptosis was observed at the same time.Results:CpG ODN(1826),when injected solely intraperitoneally, can delay the tumor growth of mouse Lewis lung cancer at some degree; The tumor growth delay was more dramatic when combined with X Ray radiation,the SER of CpG ODN(1826) was 2.09.The inhibitory rate was 24.91%when administered with CpG ODN(1826) only(P＜0.01),18.97%when dole with X Ray radiation only(P＜0.001);The inhibitory rate was 45.45% when disposed with CpG ODN(1826) combined with X Ray radiation,which was dramatically greater compared with the X Ray radiation group(P＜0.001).Compared with the control group,CpG ODN(1826) can decrease the concentration of IL-10,increase the concentration of TNF-αin the serum,advance the spleen exponent;when compared with X Ray radiation group,the difference was more dramatic(P＜0.001).With the method of TUNEL,we have detected the role of CpG on the apoptosis in vivo to find that the apoptosis rate of CpG group or X Ray radiation group was bigger than that of the control group;And,the apoptosis rate of the CpG with X Ray radiation group,59.38%,was the biggest;It was obvious bigger than that of the CpG group or the X Ray radiation group(P＜0.001).Conclusions:CpG ODN(1826) can elevate the immune function, inhibit the tumor growth,promote the apoptosis,advance the radiosensitivity of tumor dramatically by activating the immune system of mouse.