To Investigate The Correlation Between Uptake Of Tracers And The Biological Behaviors In Liver Cancer Cell Line HepG2 And Drug-resistant HepG2/4p

Liver cancer is the third cause of cancer death worldwide, is ranked second in China, seriously endangering the health of our people. With the development of molecular biology, it has been found the fundamental factor which determine the prognosis of liver cancer is the biological behavior of tumors. Modern multi-modality molecular imaging fusion technique, such as PET/CT, provides a new method to evaluate the biological behavior of HCC. In order to explore the ways of using the existing tracers to predict the biological behavior diversity of hepatocellular carcinoma cells with the same origin.. we using the feature that Rapid proliferation of cancer cells more easily lead to the differentiation of cell subsets, to establish drug-resistant strain HepG2/4p through the long-term chemotherapy intervention (5-Fu). HepG2 and HepG2/4p were brought into this research field. Some biological behavior like cell growth rate,drug-resistance were observed. Using molecular biotechnology, the biological markers include Cell proliferation protein (Ki67), Multidrug resistance gene 1 (MDR1), Glucose transporter 1 (Glutl), Chemokine receptor 4 (CXCR4) in the two groups were detected and analyzed by relative quantitative or semi-quantitative methods. The tracers as 18F-FDG,18F-FLT which reflecting different metabolic processed were used in vitro cellular uptake study in order to search the diversity and connection of uptake capability between two groups. Ultimately, Tumor-bearing nude mice models who burden different biologic characteristic HCC were performance imaging by microPET/CT system. According to the research above, some results were obtained:1. Compared with control group HepG2, drug-intervention group HepG2/4p got longer (1.56 times) doubling time, lower drug sensitivity.2. Compared with control group HepG2, The protein expression of Ki67 in HepG2/4p decreased (P<0.05), the relative expression of MDR1 increased (P<0.05). The expression of Glutl and CXCR4 was positive in two groups, but the difference was not obvious(P>0.05). Meanwhile, the tumorigenesis rate,tumor volume and growth rate of HepG2/4p are all lower.3. The 18F-FDG uptake of HepG2/4p is lower than HepG2, but the difference is not significant(P>0.05). The 18F-FLT uptake is not significant different in both two groups(P>0.05).4. In the tumor-bearing nude mice models who burden different biologic characteristic cells, HepG2 and HepG2/4p, the T/NT of imaging by single probe of two tracers (18F-FDG,18F-FLT)was no different(P>0.05).Through the study above, drug-resistant strain HepG2/4p was successfully established. The 18F-FDG uptake of HepG2/4p in vitro experiment is slightly lower than HepG2. This change showed positive trend with the expression of Ki67, showed negative trend with the expression of MDR1. But the trend only meet the expectations of chemotherapy. While there were no significant differences in two groups of molecular biological markers Glutl and CXCR4 which reflect the characteristics of malignancy and metastasis. This result may correspond to the result of tracers uptake rates which was also no significant different in two groups. The conclusion of this research may be affected by the limitation of the subject numbers,the intervention devices and periods. How to use the existing tracers to predict the biological behavior change of hepatocellular carcinoma cells with the same origin is needed to explor more.