| Oral squamous cell carcinoma (OSCC) is the most common oral cancer, accounting for more than 80% of ora cancer and for 3% -5% of systemic cancer. Oral leukoplakia (OLK) is the most common precancerous lesions .It turns to cancer in the rate from 9% to 19%, with an average duration of 8.2 years. From normal mucosa to OLK then to OSCC is a long process of development. The use of natural or synthetic chemicals in the treatment of oral precancerous lesions to block or even reverse the development of cancer is one of the means to reduce the incidence of cancer. In recent years much attention has been paid to the development and the use of Chinese medicine. Many of these traditional medicines are used for cancer treatment.Triterpenes are bitter compounds extracted from the traditional Chinese medicinal herb Ganoderma. They have a variety of pharmacological effects such as protect the liver, anti-tumor; anti-HIV-1 and HIV-1 protease activity, hypoglycemic, inhibit histamine release, inhibit of angiotensin-converting enzyme (ACE), inhibit cholesterol synthesis, analgesia, inhibit platelet aggregation, inhibit farnesyl protein transferase (FPT), anti-oxidation, inhibit eukaryotic DNA polymerase activity and so on。Among triterpenes pharmacological activity the anti-tumor effect is concerned much. The study of its anti-tumor effect is the focus of attention. Ganoderma triterpene compounds has a certain therapeutic effect for lung cancer, liver cancer, breast cancer and so on. Its cytotoxic effect, FPT inhibition, anti-oxidation and the analgesic effect have something to do with the anti-tumor effect.The mechanism of anti-tumor research of Ganoderma triterpenes is not very clear currently. The studies from the molecular level are fewer and most of them are related to the cancer in the other part of body. Most research are about the clinical or the molecule level of Ganoderma polysaccharide. Whether prevention or treatment effections of triterpenes in OSCC and OLK is not clear now. In order to find out these questions, we established the animal models of canceration induced by DMBA in the hamster. We observed the macroscopical character and pathological changes between the group given the drug and not given the drug on 6th week, 9th week and 12th week and measured bcl-2 and survivin expression from the normal buccal mucosa, epithelial hyperplasia, dysplasia, eventually to squamous cell carcinoma between the two groups.Results of observation showed that , the General conditions of experimental animal is better than control-animals.from the sixth week to twelfth week, body weight was gradually declining,but the average weigt of experimental animals was always heavier than control-animals;the hair color was better than control-animals too.the sixth week, the number 0f experimental animal whose mucosa has no obvious lesions is larger than control-animals; the ninth week,there is neoplasm in control-animals,but in experimental animals by chance; the twelfth week,most of control-animals have vegetation,or cauliflower-like,but only some of experimental animals have.all about that may be concerned with the inhibition of mucosal carcinoma of Ganoderma triterpenoids.In organization samples HE staining, we found the normal epithelial cases of experimental group were more than control group and the epithelial dysplasia rate was significantly lower than control group (P<0.05) on 6th week.On 9th week groups the moderate and severe epithelial dysplasia and carcinoma rate was lower in experimental group than in control group (P<0.05). On 12th week groups the cancer rate was significantly lower in experimental group than in control group (P<0.05). In the whole dynamic carcinogenesis observation period, the occurrence of two groups'histological difference was significant (P<0.01). The severity in experimental group was still lower than control group and the grade of cancer induced was lower. These results confirmed that the Ganoderma triterpenes inhibited OSCC.Apoptosis is an initiative of cell death process. It plays an important role in the development of tumor. This is a hot spot of today's oncology research. It provides a new idea for people particularly in the selection and mechanism of antineoplastic agents. The serious imbalance of apoptosis is destructive to the body. It has been demonstrated that the incidence of many diseases, particularly in the development of cancer, is related to the imbalance of apoptosis. The growth of tumor is due to the imbalance of proliferation and apoptosis.Bcl-2 and survivn are two important families of inhibitor of apoptosis protein (IAPs), The degree of tumor proliferation is closely related to them,but the mechanisms are different. bcl-2 mainly resistance ion imbalance that is induced by plastochondria rupture, thus blocks the cytochrome C release, may also directly suppress the activation of caspase; But survivin display anti-perishes function through directly suppresses the activeness of caspase proteinase in the bcl-2 downstream.Immunohistochemical study of bcl-2 showed that ,The positive expression rate of experimental group is only 40.0% is lower than the control group that is 86.7% obviously, looking from the concrete dyeing situation, the experimental group is lower than the control group obviously(p<0.01),it says that ganoderma lucidum can depress the expression rate of bcl-2,then inhibit the incidence rate of oral mucosa carcinoma.the expression of the development of squamous cell carcinoma from normal mucosa gradually strengthened. In the normal mucosa bcl-2 was not expressed. In OSCC positive stainings were prevalent.There were significant differences on the development from normal mucosa to carcinoma both in experimental group and control group. in the same pathological change degree, bcl-2 expression situation of experimental group and control group contrast discovery, only when paraplasm the two groups have statistics significance (P <0.05). it hints that, ganoderma lucidum display mucous membrane cancer's prevention function through bcl-2 maybe in the epidermis paraplasm stage.Immunohistochemical study of survivin showed that,The positive expression rate of experimental group is only36.7% is lower than the control group that is 86.7%, concrete dyeing situation, the experimental group is lower than the control group obviously(p<0.01),it says that ganoderma lucidum may reduce the survivin expression quantity in the mucous membrane organization, thus degrade the incidence of carcinoma on hamsters cheek pouch. Follows the aggravation of pathological change degree, survivin expression quantity increases gradually(experimental group: P<0.01,control group P <0.05). in the same pathological change degree, surviving expression situation of experimental group and control group contrast discovery, only when epith. simple hyperplasia and paraplasm the two groups have statistics significance (P <0.05). it hints that, ganoderma lucidum display mucous membrane cancer's prevention function through survivn maybe in the epidermis simple hyperplasia and paraplasm stage.Survivin as a formidable family of IAPs,possibly participated in oral cancer's formation and development directly, possibly through suppress cell perishes, thus urges tumour cell's further multiplication worsening; Bcl-2 possibly reduce tumor cell apoptosis, extension tumour cell's life, so the cell number increase, bcl-2 participates in oral cancer's occurrence development. Although Survivin is different from the function mechanism of bcl-2, but they all can affect Caspase to suppress cell perishes. Most fatal signal promote apoptosis induced by the effect of Caspase, it is a hint that Ganoderma Triterpenoids can promote of apoptosis of tumor cells through bcl-2, survivin role in Caspase.It effect mainly in the stage of epithelial hyperplasia and dysplasia .These results suggest that Ganoderma triterpenes has prevention and treatment effect in oral premalignant lesions. This provide us a new way of thinking the treatment for oral squamous cell carcinoma. It has broad application prospects used as a preventative and auxiliary treatment of cancer. Ganoderma triterpenes has complex mechanism and need further study. |
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