| Objective To treat the LA795 lung adenocarcinoma of mice transplantable tumor using tyrosine activating enzyme inhibitor-SU 11248, observe the transplanted tumor growth and the shift inhibitory action, and discuss the mechanism of the anti-tumor growth and shift of SU11248.Method T739 mouse transplanted tumor model were duplicated by lung adenocarcinoma cells LA795.40 T739 male mouse that vaccinated high transferability of the LA795 lung adenocarcinoma cells were randomly divided into the control group, the negative treatment group (trimethylene glycol 0.2ml+physiological saline 0.2ml), the low dose SU11248 group (SU11248:30mg/kg), the dosage SU11248 group (SU11248:40mg/kg) and the high dose SU11248 group (SU11248:50mg/kg). It was started to apply drugs the intervention after vaccinated for 4 days, and untoward effect and the tumor growth situation were observed at the medication period, hypodermic transplant lump biggest major axis (a) and transverse diameter (b) were surveyed with Vernier caliper every 5 days, tumor volume were counted, then tumor growth suppression rate were computed, and then tumor growth curve were drew; Vaccinated for 24 days, all mouse were killed by escaping the neck mortar, hypodermic transplant lump were dissected and weighed, the average weight of each group of transplant lump and the suppression rate were counted respectively; The shift lump tubercles of lung were counted by using naked eye and dissecting microscope. Then the transplanted tumor and the lung shifts were fixed, the paraffin wax were embedded. The slices of transplanted tumor and lungs shifts in each group were dyed by HE and observed. VEGF-C, FLK-1 and PCNA expression situation of transplanted tumor were examined in immunity groups. Transplanted tumor cell apoptosis of mouse in each group were examined by the home position perishes the TUNEL law. VEGF-C and FLK-1 mRNA expression in transplanted tumor were examined by RT-PCR.Results (1) At the start of the experiment, the mouse body weight of each group were the approximate same, the difference were not significant(P>0.05). At the end of the experiment, the mouse body weight of the control group and the negative control group were obviously dropped, compared to prior treatment, the difference were significant(P<0.05). The mouse body weight of various monitoring groups had dropped various degrees, and the high monitoring group was the lowest. Compared to prior treatment, the difference of the high monitoring group was not significant(P>0.05), but the average monitoring group and the low monitoring group was(P<0.05). After the treatment, compared to the control group and the negative control group, the differences of the average monitoring group and the high monitoring group were significant(P<0.05), but the low monitoring group was not(P>0.05). And the differences were significant between various monitoring groups(P<0.05). After the vaccination, tumorgenesis was 100%, each group of hypodermic transplant lump's volume increased gradually, the tumor became the partial knot nodular. At the vaccination of the day 1-4th, the transplant lump grew the basical same; at the day 14-24th, transplant the lump of the control group and the negative control group grew obviously quicker than in various monitoring groups, but the high monitoring group grew slower. (2) Transplanted tumor weight weren't changed significant in control group and negative control group. Transplanted tumor weight of each dose group decreased, the high-dose group was the lowest. While the tumor weight inhibitory rate was increased the highest in high-dose group. Compared with the control group and negative control group, the difference was significant(P<0.05). Among the various dosage groups, the difference was significant(P<0.05). (3) The number of lung metastatic nodules were reduced in turn in the control group, negative control group, low-dose group, middle dose group and high dose. The differences between middle-dose group and control group, negative control group and low-dose group were significant(P<0.05). The differences between high-dose and the control group, negative control group, low-dose group and middle-dose group differences were significant(P<0.05). But The differences between control group, negative control group and low-dose group were not significant(P>0.05). The inhibition rate of the metastatic nodules in control group, negative control group, low dose group, middle dose group and high dose group were increased in turn. Compared to the control group and negative control group, there were no significant difference between each dose groups(P>0.05). Compared to control group and negative control group, the differences of each dose group were significant differences(P<0.05). (4) Light microscope were used to observe cells, in the control group and the negative control group, transplanted tumor cells maintained the condition and the cancer cell original heterogeneous type at the vaccination, there were blood vessel proliferation in the cancer tissues, especially in mesenchymal and tumor edge. The varying degree of draw back changes of cancer cells were presented in various monitoring groups, necrosis area was obvious, blood vessel ingredient were reduced in mesenchymal. Through HE dyed, the volume of apoptosis cells reduced and distorted, the nucleus dyed the thicker blue color, and compacted spherical or apoptosis body appeared; in the control group and the negative control group the apoptosis cells of transplanted tumor were few, various monitoring groups were increased, the high monitoring group was the most. (5) In control group and negative control group, tumor cell proliferation index and tumor cell apoptosis rate was roughly the same, the difference was no significant(P>0.05); tumor cell proliferation index of each dose group was lower than the control group and negative control group, while the high rate of tumor cell apoptosis in the control group and negative control group, compared with the two groups, low-dose group did not differ significantly(P>0.05), middle-dose group and high-dose group differences were significant(P<0.05); various doses of tumor cell proliferation index between the two groups showed the reverse changes in a dose, the dose the greater, the proliferation index the lower, the differences were significant(P<0.05). Various doses of tumor cells apoptosis rate between the two groups showed a positive change in dose, dose the greater, the rate of tumor cell apoptosis the greater, the differences were significant(P<0.05). (6) MVD and VEGF-C and FLK-1 protein expression of the tumor in the control group and negative control group were roughly the same, there was no significant difference(P>0.05); but in each dose group, compared with the control group and negative control group, MVD and VEGF-C and FLK-1 protein expression, low dose group did not differ significantly(P>0.05), middle-dose group and high dose group were significant(P<0.05); each dose group and MVD between VEGF-C and FLK-1 protein expression changed inversely with the dose, the dose greater, the MVD, VEGF-C and FLK-1 protein expression the lower, the difference between each dose group were significantly(P<0.05). (7) VEGF-C expression and MVD in the all mice transplanted tumor tissues showed changes in the same direction and linear correlation analysis showed positive correlation. (8) VEGF-C and FLK-1 protein expression and proliferation index and lung surface metastatic nodules in the all mice transplanted tumor tissues showed the same direction changes and linear correlation analysis showed positive correlation, while VEGF-C and FLK-1 protein expression and tumor cell apoptosis showed negative correlation.Conclusion SU11248 could be through inhibiting lung adenocarcinoma LA795 in mice transplanted tumor in VEGF-C and FLK-1 protein expression, reduce micro vessel density, thereby inhibit tumor growth and metastasis of tumor cells and promote apoptosis of tumor cells transplanted tumor. |
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