[Effects of indole-3-carbinol on the outcome of tumor and the changes of anti-oxidative system in null mice grafted with nasopharyngeal carcinoma].
OBJECTIVE
To observe the effects of indole-3-carbinol (I3C) on the outcome of the tumor as well as the changes of the anti-oxidative system in null mice grafted with nasopharyngeal carcinoma.


METHODS
48 BALB/c null mice were divided by means of random number table into control group (0.5% sodium carboxyl methyl cellulose), low dosage (0.02 g/kg), middle dosage (0.1 g/kg) and high dosage (0.5 g/kg) of I3C. The mice were administered with different solutions by gavage for 10 days before CNE1 cells were inoculated subcutaneously into the back (near the armpit) of the nude mice, then the solutions were continually administered by gavage. The tumor volume was measured and the tumor inhibitory rate was calculated. The level of malondialdehyde (MDA), the activity of superoxide dismutases (SOD), the activity of glutathione peroxidase (GSHPx) and the expression of cleaved caspase-3 were determined on the 31th day of the study.


RESULTS
I3C could reduce the tumor volume [the tumor volumes of the control group, the middle dosage group and the high dosage group were (4.13 +/- 0.53) x 10(-6) m(3), (3.14 +/- 0.71) x 10(-6) m(3), (2.72 +/- 0.29) x 10(-6) m(3)], as compared with the control, the shrinkage of tumor volume of the middle dosage group and the high dosage group were significant (the t valued at 0.990 and 1.510, P < 0.01). The tumor inhibitory rates of 3 groups were 3.8%, 20.5% and 34.9%, respectively. The contents of MDA in the tumor tissue tended to decrease [the values of control group, the low dosage group, the middle dosage group and the high dosage group were (31.29 +/- 2.51) x 10(-6) mol/L, (30.12 +/- 2.37) x 10(-6) mol/L, (23.32 +/- 1.93) x 10(-6) mol/L, (16.45 +/- 1.43) x 10(-6) mol/L] (F = 98.752, P < 0.01), and that of the high and the middle dosage group could obviously be reduced (t = 8.970, 14.840, P < 0.01) as compared with the control. The activity of SOD seemed to be elevated according to the increase of I3C dosage [the values were (387.24 +/- 23.16) x 10(3) U/L, (399.37 +/- 34.45) x 10(3) U/L, (431.63 +/- 31.24) x 10(3) U/L, (476.45 +/- 44.67) x 10(3) U/L] (F = 53.444, P < 0.01). When compared with the control, the SOD activity of the middle and the high dosage group be obviously increased (t = 44.390, 89.210, P < 0.01). I3C could also elevate the GSHPx activity [the GSHPx values of the four groups were (226.98 +/- 18.35) x 10(3) U/L, (234.65 +/- 15.59) x 10(3) U/L, (247.72 +/- 22.73) x 10(3) U/L, (300.37 +/- 26.02) x 10(3) U/L] (F = 25.916, P < 0.01). The GSHPx of the high dosage group was enhanced remarkable (t = 73.390, P < 0.01) as compared with the control. The expression of cleaved caspase-3 (relative molecular weight = 19 000 000) seemed to be elevated according to the increase of I3C dosage and the relative expression levels of which were 0.87 +/- 0.01, 0.97 +/- 0.01, 1.02 +/- 0.06 and 1.14 +/- 0.02 (F = 39.864, P < 0.01). When compared with the control, the elevation of this kind of cleaved caspase-3 was considered statistical significant (the t values were 0.100, 0.086 and 0.303, respectively, P < 0.05). When I3C dosage increased, the expression of cleaved caspase-3 (relative molecular weight = 17 000 000) seemed to increased too [the relative expression levels of which were 0.00 +/- 0.00, 0.05 +/- 0.02, 0.11 +/- 0.02, 0.20 +/- 0.02 (F = 56.629, P < 0.01)], and the increase of this kind of cleaved caspase-3 was esteemed significantly as compared with those of the control (the t valued at 0.046, 0.103 and 0.193, respectively, P < 0.05). Linear correlate analysis showed that the correlation coefficients between the shrinkage of tumor volume and the expression of the two kinds of cleaved caspase-3 protein was -0.732 (t = 3.404, P < 0.01) and -0.901 (t = 6.642, P < 0.01).


CONCLUSIONS
I3C could reduce the growth of tumor, the mechanism underlie it could be related to the decrease of the content of MDA as well as the elevated levels of SOD, GSHPx, and perhaps could be related to the apoptosis transduced by cleaved caspase-3.
Guangzhou Center for Disease Control and Prevention, China.
Wei
W
Zhu
Guang-yu
GY
Yang
Quan-xin
QX
Zhang
Jun-tao
JT
Li
Wen-xue
WX
Li
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009366:Neoplasm Seeding; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism
D007211:Indoles; D008315:Malondialdehyde; C016517:indole-3-carbinol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase