| Liver cancer,a malignant tumor that occurs in the liver,is one of the most common malignancies in the world with a high incidence and mortality.Many studies suggested that the main ingredients of many traditional Chinese medicine has antioxidant and anti-cancer effect.However,it has not been confirmed whether these Chinese medicine decoction has an inhibitory effect on hepatocarcinoma,because the composition of Chinese medicine is very complicated.Based on these backgrounds,to clarify the modifying effects of siraitia grosvenorii(SGE),taraxacum,codonopsis and astragalus decoctions on early stage of hepatocarcinoma in SD rats,we conducted any pharmacological test of these decoctions.In present study,we made the early stage hepatocarcinoma animal model using diethylnitrosamine(DEN)and Piperonyl butoxide(PBO)as initiator and promoter,respectively.Experiment ?: Study on effects of SGE or taraxacum decoctions on early stage of hepatocarcinoma in SD rats.Experiment ?:Study on effects of codonopsis or astragalus decoctions on early stage of hepatocarcinoma in SD rats.Experiment ?: Study on effects of codonopsis and astragalus composite decoctions on early stage of hepatocarcinoma in SD rats.In the present study,Five-week-old male Sprague-Dawley(SD)rats(80-100 g B.W.)were purchased from Chongqing Academy of Chinese Materia,Experimental Animals Institute,maintained in an air-conditioned room with a twelve-hour light/dark cycle(room temperature,24 ± 2 ?;relative humidity,55% ± 15%),and given free access to a powdered basal diet and tap water.After a one-week acclimatization period,a medium-term liver carcinogenesis bioassay(Ito et al.2003)was performed according to the following procedure.All animals were initiated with an intraperitoneal injection of DEN(200mg/kg body weight,dissolved in saline),and divided into 3 groups.All animals of 2~3 groups were given a diet containing 0.5% PBO for 6weeks starting two weeks after DEN initiation.In addition,animals of 3 group were subjected to repeated oral administration Chinese medicine decoction(CMD)for 6 weeks with PBO(Group 1: DEN alone;Group 2:DEN+PBO;Group 3: DEN+PBO+CMD).All animals were subjected to two-thirds partial hepatectomy 1 week after PBO treatment.Six animals died after partial hepatectomy,while 34 animals survived.The results are as follows:1.Effect of SGE,Taraxacum,Codonopsis or Astragalus decoctions on early stage of hepatocarcinoma in SD ratsNo remarkable changes in general appearance were observed in treated groups during the experimental period.Final body weights were significantly decreased in the PBO-treated groups.In addition,absolute and relative liver weights in the PBO-treated groups significant increased as compared to the DEN alone.However,there was no significant difference between Chinese chemical decoction groups and DEN+PBO group.In histopathological examination,there is a reduce tendency the incidence of single cell necrosis and vacuolar degeneration of hepatocytes in Chinese chemical decoctions groups as compared to the DEN+PBO group.In immunohistochemical staining,the number and areas of GST-P-positive foci in the SGE,Codonopsis or astragalus decoction groups showed a decrease tendency compared to DEN+PBO group.Especially,the number of GST-P-positive foci in the astragalus decoction group significantly decreased compared to DEN+PBO group.On the other hand,the number of Ki67 positive hepatocytes in all Chinese chemical decoction groups remarkably decreased compared to DEN+PBO group.In molecular biological examination,a significant decrease in the mRNA expression of Nqo1 was observed in the liver of rats treated with SGE or taraxacum decoctions.However,there was no significantly differences in the expression lever of other genes such as Cyp1a1,Cyp1a2,Gpx2,CcnD1,that is related to PBO induced hepatocarcinogenesis,between DEN+PBO and Chinese chemical decoction groups.The above results show that SGE,taraxacum,codonopsis or astragalus decoctions has a strong inhibition of cell proliferation activity.In particular,the Astragalus decoction also have a significant inhibitory effect on the number of preneoplastic lesion.On the other hand,the SGE or taraxacum decoctions may be effect PBO induced hepatocarcinogenesis through suppressing the expression level of Nqo1.These results suggested that SGE,taraxacum,codonopsis or astragalus decoctions may be used with anti-cancer therapy.However,the anti-cancer effect of these decoction is relatively weak,further studies are necessary to clarify the possible mechanism underlying the anti-cancer of these decoctions in SD rats.Therefore,reasonable combination of thesedecoction may be more effective.2.Effect of Codonopsis and Astragalus combination decoctions on early stage of hepatocarcinoma in SD ratsNo remarkable changes in general appearance and food intake were observed in treated groups during the experimental period.Final body weights were significantly decreased in the PBO-treated groups.In contrast,absolute and relative liver weights in the PBO-treated groups significant increased as compared to the DEN alone.In immunohistochemical staining,the number and areas of GST-P-positive foci in the Codonopsis and astragalus combination decoction group remarkably decreased compared to DEN+PBO group.Especially,the area of GST-P-positive foci significantly decreased compared to DEN+PBO group.On the other hand,the number of Ki67 positive hepatocytes in combination decoction group showed a decrease tendency compared to DEN+PBO group.In molecular analysis,a significant decrease in the mRNA expression of Abcc3 was observed in the liver of rats treated with codonopsis and astragalus combination decoctions as compared to the DEN+PBO group.These results suggested that the codonopsis and astragalus combination decoction can inhibits cell proliferation and neoplastic lesions.In addition,the regulation of combination decoction to Abcc3 was involved in the mechanism of anti-cancer of this decoctions in SD rats.In conclusion,the decoctions of SGE,taraxacum,codonopsis or astragalus and codonopsis and astragalus combination decoction have a strong anti-cell proliferation activity,and these effects contributed to the development of neoplastic lesions.In addition,these results suggested that the regulation of SGE to Nqo1 and codonopsis and astragalus combination decoction to Abcc3 may also be involved in the mechanism of their anti-cancer.These results not only provide a scientific evidence for the clinical therapy of hepatocarcinoma,but also provide impotant information for the development of tranditional Chinese medicine.medicine. |
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