In Vivo And In Vitro Studies Of Natural Product Terphenyllin On Pancreatic Cancer

Objective: Pancreatic cancer(PC) is a highly malignant disease with a poor prognosis and a5-year survival rate of no more than 5%.It is known as the “King of Cancer”.Surgical resection combined with chemotherapy is pancreatic cancer.At present,the most important treatment method,but because patients have no specific clinical manifestations in the early stage,only about 20% of patients can undergo surgery.In addition,chemotherapy drugs have large side effects and are expensive,so it is urgent to find safe and effective treatment drugs.There are many kinds of natural products,unique structures and bioactive diversity,which are important sources of new drug research.The natural product Terphenyllin is a natural p-terphenyl metabolite isolated from the coral-derived fungus Candida.It has a certain cytotoxicity,but there is little research on its antitumor effect.The effects of pancreatic cancer proliferation,apoptosis,migration,invasion,and the growth of pancreatic tumors in situ.Method:1.Terphenyllin in vitro study of pancreatic cancer1.1 The effect of Terphenyllin at different concentrations on the proliferation of normal pancreatic cells and a variety of pancreatic cancer cells was detected by the CCK-8 method,and the more sensitive pancreatic cancer cells were selected for determination.Plate colony formation experiments were used to detect the inhibitory effect of Terphenyllin at different concentrations(0,20,50,200μmol/L)on the growth of two sensitive pancreatic cancer cells.1.2 The effects of Terphenyllin on the apoptosis of pancreatic cancer cells were detected by flow cytometry.1.3 The effect of Terphenyllin on apoptosis-related proteins was detected by Western Blot method.1.4 The effect of Terphenyllin on the migration and invasion of pancreatic cancer cells was tested by migration and invasion experiments.2.In vivo study of Terphenyllin on pancreatic cancer2.1 Terphenyllin was used to treat Nod-scid pancreatic carcinoma in situ mice,and the effect of Terphenyllin on tumor signal intensity of pancreatic cancer mice was observed by in vivo imaging technology.At the same time,the body weight was measured every two days,and the mouse status was observed.2.2 After the administration,observe the metastasis of the organs with a live imager and stain with HE to observe the effect of Terphenyllin on the tumor growth of Nod-scid pancreatic carcinoma in situ mice.Results:1.In vitro study of terphenyllin on pancreatic cancer1.1 CCK8 test results show that compared with pancreatic cancer cells,normal pancreatic cells are less sensitive to Terphenyllin,and more sensitive Panc1 and HPAC cells were selected from pancreatic cancer cells for subsequent research.The plate cloning experiment showed that with the increase of drug concentration,the number of clones decreased significantly,indicating that Terphenyllin significantly inhibited the proliferation of Panc1 and HPAC cells.1.2 Apoptosis results showed that with the increase of drug concentration,the total apoptotic rate gradually increased,indicating that Terphenyllin can promote apoptosis in Panc1 and HPAC cells.1.3 The results of Western blot showed that as the drug concentration increased,the related apoptotic proteins PARP,Caspase7,Bcl-2,etc.all changed.1.4 The results of migration and invasion experiments showed that Terphenyllin can inhibit the migration and invasion of pancreatic cancer cells Panc1 and HPAC.2.In vivo study of Terphenyllin on pancreatic cancer2.1 During the administration,the results of in vivo imaging showed that the tumor growth trend of the administration group was slower than that of the control group.There was no significant difference in body weight,mental state,and activity between the administration group and the control group.2.2 After the mice were sacrificed,the liver,heart,spleen,lung,kidney,and brain organs of the mice were dissected,and the signal intensity of the organs was observed separately.The heart,spleen,kidney,and brain organs did not metastasize.Five of the six mice developed liver metastasis,and four of them developed lung metastasis.In the treatment group,two mice developed liver metastasis and one mouse developed pulmonary metastasis.The results of HE staining showed that the liver,heart,spleen,lung,kidney,and brain organs were consistent with the above-mentioned in vivo imaging results.Conclusion: This study verified the mechanism of the natural product Terphenyllin,both in vivo and in vitro.In vitro experiments suggest that Terphenyllin can effectively inhibit the proliferation,migration,and invasion of pancreatic cancer cells,and can promote the apoptosis of pancreatic cancer cells.In vivo experiments have shown that Terphenyllin can effectively inhibit the growth of carcinoma in situ in Nod-scid mice.The natural product Terphenyllin may be used as a potential drug for the treatment of pancreatic cancer,providing ideas for the clinical treatment of patients with pancreatic cancer.