Experimental Studies On Therapy For Lewis Lung Cancer In Mice With Interstitial Implantation Of ～(125)Ⅰ Seeds And Tradition Teletherapy

Objective: Nowadays, malignant tumor has become the most important disease which threats human being's health and life. Operation is the optimum method. But most of the tumour patients of clinical, who make a definite diagnosis at present, are in advanced stage. They have no way to be cured by operation. While, the person curative ratio is lower than 50% even if carrying out by operation. The research data demonstrated that, 45% patient may cure after the complex therapy, 18% is cured by the radiotherapy. Approximately 70% of Chinese tumour patients have to accept radiotherapy, and about 50% tumour patients recent discovered in Japan use radiotherapy, 50%-60% patients in USA recent discovered use radiotherapy[1]. The important of radiotherapy is looked upon by people day by day. This topic has studied the therapeutic action of the electron ray to mice-transplanted tumor and their mechanism. Take the mice-transplanted tumor of Lewis lung cancer as the model, treat by the fact that the implantation of ¹²⁵I seeds and tradition teletherapy, observing mice-transplanted tumor's volume, and PCD rate of the tumor cell, protein expression about the cell PCD and the mouse radioactive damage, discussing furtherly about radioactivity ¹²⁵I seeds and tradition teletherapy killing and wounding tumorous mechanism, providing the basis for the clinical application of curing tumor.Methods: 1 Build up the model of transplantation of tumor Lewis lung cancer in 48 mice, observing the growth regulation of the tumor and behavior condition of the mice. 2 The mice used in the experiment were randomly divided into 6 groups. The group of ¹²⁵I seeds: A group; B group. The group of teletherapy: C group; D group. The control group: E1 group; E2 group. Each group with 8 mice. Implant 1.0mCi radioactivity ¹²⁵I seeds in A and B group, on the grounds of the formula that AAPM stipulates, On the basis of emit dosages, radiation distance, radiation time, figure out the time that the organization which from the seeds is 0.5cm absorption dosages reach 5Gy, 10Gy respectively for 4 day and 9 day, then draws materials respectively form the 4th, 9th day. The group of teletherapy is irradiated with routine radiotherapy treat. The linear accelerator's energy for 6MV, dose rate to be 250cGy/minutes, be 1 meter from irradiating source, the C group 1st day irradiates 5Gy, draw the materials in fourth day; the D group irradiates 5Gy in 1st day, another 5Gy in fifth day, draw the materials in ninth day. The E1 and E2 group draw the materials respectively form the 4th, 9th day. 3 Around processing uses Vernier Caliper to survey the most major axis(a) and most minor axis(b) of the tumor every day, according to V=0.2×ab2 computation tumor volume(mm³), The tumorous inhibition ratio (IR)=(Control group-Treated group) the average tumor volume/the mean control group's tumor volume, plan tumor growth curve. 4 Researching the circumstance of tumor cell apoptosis using the method of flow cytometry (FCM). 5 By immunohistochemistry, detecting the tumour organizes protein expression about Bcl-2, Bax, Caspas-3, Caspas-9, carries on the contrast studying, preliminary understanding the mechanism of radioactive ray to killing and wounding the tumor. 6 To obtain the blood by orbital vein for blood routine analysis for WBC .7 The lung of the mice was observed by pathological section for the radioactive damage of the lung organizes.Results: 1 The tumor body can be touched after hypodermic injection Lewis lung cancer cells for 4-6days. For nearly 12 days, the tumor diameter is 1.0cm,the mice can be used in the experiment. The tumor body of control groups increased, for 22 days the tumor diameter to continue increased, the center became quaggy (It is necrosis tumour tissue that can be proved by stab). The effect shows in A , B , C , D group,ray can comparatively minification mice-transplanted tumor by killing and wounding. In fourth day, the inhibiting rate in A, C group respectively are 63.38%, 93.21%; in ninth day, the inhibiting rate in B, D group respectively are 85.73%, 99.55%. In the group A and C, the tumour volume is diminished obviously compared with control group E1, have statistics significance(P<0.05). In the group B and D, The tumour volume is diminished obviously compared with control group E2(P<0.05). 2 Discovering that radioactive ray can induce the tumor cell apoptosis after radiation by FCM. In the group A and C, the tumour PCD rate compared with control group E1, have statistics significance(P<0.05), there are obvious differences in statistics(P>0.05) between group A and B. In the group B and D, the tumour PCD rate compared with control group E2, have statistics significance(P<0.05), there are obvious differences in statistics(P>0.05) between group C and D. 3 The related gene about apoptosis Bcl-2, Bax, Caspase-3, Caspase-9 are expressed in the cytoplasm of the tumor. Contrast protein express of Bcl-2, Bax, Caspase-3, Caspase-9 between radioactivity ¹²⁵I seeds group and the group of teletherapy shows: In the group A and C ,The tumour protein of Bcl-2 express depressed obviously compared with control group E1, have statistics significance(P<0.05). In the group B and D ,the tumour protein express is depressed obviously compared with control group E2(P<0.05);the tumour protein express in group B is higher than in group A(P<0.05), the tumour protein express in group D is lower than in group C (P<0.05). In the group A and C, the tumour protein of Bax, Caspase-3, Caspase-9 express increased obviously compared with control group E1, have statistics significance(P<0.05). In the group B and D, the tumour protein express is increased obviously compared with control group E2(P<0.05); Of the total, the tumour protein express in group B is higher than in group A(P<0.05), the tumour protein express in group C is higher than in group D(P<0.05). 4 The blood routine analysis shows mice with tumor WBC decreased to follow the radioactive ray dose increased. In the group A and B, the mice WBC compared with control group have no statistics significance(P>0.05), In the group C and D, the mice WBC is lower obviously compared with control group(P<0.05), In the group D, the mice WBC is lower obviously compared with control C group(P<0.05). 5 There is no conspicuous radiation damage in the lung by hematoxylin and eosin stain in the group A and B. In the group C and D, the lung blood vessel especially the micrangium injured and formed hyperemia, edema and inflamm cell infiltration, the lung periplast thicken, pulmonary alveoli changes small. The pulmonary alveolusâ…¡type cell neorobiosis and amotic, lymphatic vessel extends and to form asphyxial membrane, the lung connective tissue hyperplasia, fibrosis and hyalinization.Conclusions: 1 The lung Lewis cancer animal model is suitable for radioactive seeds to cure lung cancer for biology effects, the methods is simple, and are easily handling and observing 2 Both the ¹²⁵I seeds interstitial brachytherapy and tradition teletherapy can cause the volume of mice-transplanted tumor to small.3 It can be discovered by FCM that ¹²⁵I seeds interstitial brachytherapy and tradition teletherapy can cause the cell of mice-transplanted tumor to PCD.4 The electronic ray (the ¹²⁵I seeds, teletherapy) causes the tumor cell to apoptosis is through changing the gene of the tumor cell,cell apoptosis is one of the important mechanism for ¹²⁵I seeds interstitial brachytherapy and tradition teletherapy to cure tumour. 5 There is obviously radiation damage in tradition teletherapy groups,but it can not detected radiation damage in the group of ¹²⁵I seeds.