| Background & PurposePrimary liver cancer (PLC), the world’s fifth common malignant tumor, accounted for the third for the word’s common malignant tumor leading to death. According to analyzing lots of clinical data, it concludes that hepatocellular carcinoma (HCC) is obviously different with intrahepatic cholangiocarcinoma (ICC) in biological characteristics, comprehensive treatment methods and the prognosis. HCC is over 90% of the proportion of primary liver cancer. The research is focused on HCC. In our country, chronic hepatitis B virus is the main pathogenic factor to HCC. In recent years, the inoculating of HBV vaccine reduces HBV infection in the infant, but our country is HBV infection epidemic areas, according to relevant statistics, the number of hepatitis B surface antigen (HBsAg) is about 100 million people, which the patients with chronic HBV is about 20 million people. Some chronic HBV patients don’t control the disease, it will gradually develop to cirrhosis,10-15% of the cirrhosis patients will develop to the cancer. Now more than 600 thousand new PLC cases around the world every year, only our country is over 300 thousand patients, accounting for 50%. It shows that PLC is still a serious damage to the human health especially for Chinese. About 70-80 percent of PLC patients are in common with cirrhosis, which increases the difficulty for the treatment of PLC. Due to the specificity of the liver structure, the tumor will spread in intrahepatic by the portal vein, it will transfer to anywhere by the blood vessels and lymphatic metastasis. Liver cancer diagnosis relies mainly on the history, elevated blood AFP, and liver enhanced CT or MRI imaging findings, CT or MRI tumor reinforcement hint "fast into fast out" image. For hepatocellular carcinoma, lacking specific clinical symptoms, so the patients are diagnosed as middle or late period, according to relative data, only 20 percent of the PLC patients could have the opportunity to surgery. Now surgery is only treatment for PLC patients can obtain the long-term survival, the early PLC patients after surgical resection, 5 years survival rate can reach 85%. But for the middle-late or final stage of PLC patients, who had lost the chance to operating, chemotherapy, radiotherapy and biological treatment may prolong the survival, now the development of targeted drμgs, sorafenib, which can improve the prognosis for the middle-late PLC patients. But the adverse reaction of chemotherapy drugs, the resistance to drugs and the high cost for the targeted drugs and its significant side effects, especially the patients with cirrhosis will increase the damage of liver function. In clinic, we found that sorafenib can’t reach the satisfied effects for the HCC patients. Thus limits sorafenib widely use in clinical. So it is necessary to further explore the new treatment of liver cancer drugs or sensitivity to chemotherapy drugs.elemene is one of the active components extracted from the traditional Chinese medicine herb Rhizoma zodiariae, the structure is similar to paclitaxel, which was approved as one kind of antitumor drμg by the state. As the effect antitumor components,elemene has abundant resources and it’s price is relatively cheap comparing with other chemical synthetic drμgs. There are many papers to report that elemene has obviously antitumor effect on many tumors, like esophageal cancer, gastric cancer, lung cancer, ovarian cancer and other tumors, elemene mainly inhabits tumor growth by inducing tumor cell apoptosis and inhibiting tumor cell transfer. According to clinical materials, we found its toxicity is very small for the patient’s liver, kidney function and bone marrow. For the PLC patients with cirrhosis, the liver function reserve is poor, who couldn’t tolerate chemotherapy or radiation therapy and should be treated with promoting liver function and using the small application effect on liver function of antitumor drμgs to inhibit the growth of tumors, which earn little time to make the liver recovery, thus patients may have opportunity to accept other treatment. The current treatment ofelemene in PLC is mainly by transcatheter arterial chemoembolization with other medicine, the effect is better than chemotherapy drμg alone. But now how about elemene inhabit the growth of HCC and the mechanism of elemene anticancer remains unclear, which is the problem to discuss. This experiment is to eatabilish the liver cancer model in mice and observeelemene anticancer effect of HCC.Methods & ResultsThe experiment mainly consists of two parts.1. Vitro experiment in elemene of liver cancer cellsa. CCK8 observes the antitumor effect on the H22 cell line by different concentration of elemene and calculate the median lethal dose is 30μg/ml.b. The apoptosis significantly increased which treated with elemene 24 hours later by the flow cytometry experiment.c.The migration ability of H22 cell was decreased obviously after treated with the elemene by the Transwell experiment.d. AKT mRNA expression quantity is decreased for the H22 cell and which treated with elemene comparing with which not treated by the PCR, but the result don’t have the statistical significance.e. P- AKT protein is decreased for the H22 cell which treated with elemene by Western-blot method, while there is no change in AKT.2. Vivo study in elemene of hepatocellular carcinomaa. building model of liver cancer in C57 miceThe H22 liver cancer cell line was revived and cultivated in vitro, which was manufactured in cell suspension with PBS liquid. The cell suspension was injected to the Kuming mouse enterocoelia, the cancer cell ascites was needed to developed to the third generation, then subcutaneous injection in the mouses’ left anterior axilla. When the subcutaneous tumor growed to 1 centimetre, taken off completely and cutted into 1mm size tumor pieces,which were transplantated in C57 mouse liver.b. Dividing into groupsThe mice models were randomly divided into four groups, each group was 10 mice, physiological saline、elemene、Tegafur Gimeracil Oteracil Potassium Capsule(s-1) and S-1+elemene. The mice were filled once a day in the second day after the model established. c. Vivo study in elemene of hepatocellular carcinomaThe mice were filled once a day in the second day after the model established. The color of the hair in mice and general living conditions were observed among the two weeks.Two weeks later, weighing the mice and measuring the size of orthotopic transplantation tumor. The results showed that B、C、D group was statistically significant comparing with A group in liver tumor size, there is no statistically significant among B、C and D group. But weight in C group was lighter than A、B、 D group, there is no significance between A、B、D group. Tumor tissue sample was fixed by formaldehyde, HE staining to observe the characteristics of liver tumor as well as the satellite around the liver tumor. The results showed that there were satellite in A group, not in B、D group.ConclusionThe experiments further confirmed that elemene played a role in anticancer mainly by inhibiting tumor cell proliferation、matastasis and inducing tumor cell apoptosis. This experiment argued that elemene achieve anticancer effect may be by lowering the p-AKT expression. This subject successfully built the mice model of orthotopic liver cancer transplantation,more than 90 percent mice model was successful. The side effects were far less than the s-1,and the anticancer effect is similar with the s-1.elemene has less side effects and studies sμggest that elemene could significantly improve the sensitivity of the chemical medicine for the primary liver cancer. |
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