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Folate metabolism resistance in the signal path with NPC Correlation

Author: JiangCuiHong
Tutor: TanGuoLin
School: Central South University
Course: Department of Otolaryngology Head and Neck Surgery
Keywords: Nasopharyngeal Taxol Resistant cell lines Folate metabolism genes
CLC: R739.63
Type: Master's thesis
Year: 2008
Downloads: 87
Quote: 1
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Abstract


Nasopharyngeal carcinoma is common otolaryngology head and neck cancer to radiotherapy, chemotherapy can improve the prognosis, but during chemotherapy prone to tumor cell resistance to chemotherapeutic drugs, nasopharyngeal cancer chemotherapeutic drug resistance is the current hot issue. Our previous study found that folate receptor 1 gene in nasopharyngeal chemotherapeutic drug resistance plays an important role, therefore investigate folate receptor signaling and metabolic pathways, to elucidate the nasopharyngeal chemotherapy drug resistance is important. Objective: To study the key enzyme in folate metabolism pathway folate receptor gene 1 (FOLR1), dihydrofolate reductase (DHFR), serine hydroxymethyl transferase (SHMT), thymidylate synthase (TS) and nasopharyngeal resistance paclitaxel chemotherapy, to explore the nasopharyngeal molecular mechanisms of drug resistance to chemotherapy. Method: 1. Using colony formation assay (colony formation assay) detection of folic acid in nasopharyngeal carcinoma parental cell line CNE-1 and the corresponding impact resistant cell lines CNE-1/Taxol. (2) human nasopharyngeal carcinoma cell line CNE-1, HNE-2 cells and the corresponding paclitaxel-resistant cell lines CNE-1/Taxol, HNE-2/Taxol as the research object, using reverse transcription polymerase chain reaction (RT- PCR) determination of folate metabolism pathway key enzyme FOLR1, DHFR, SHMT, TS in nasopharyngeal carcinoma cells resistant to the parental cells and beads expression differences were observed with nasopharyngeal Resistant. 3 Immunohistochemical SP method FOLR1 in nasopharyngeal carcinoma and normal nasopharyngeal tissues difference. Results: 1. Lack of folic acid resistant cells cultured colony inhibition rate was significantly higher than the parental lack of folic acid cultured colony inhibition rate (P <0.05), the growth of resistant cells than the parental cells more dependent on folic acid. 2 was detected by RT-PCR folate metabolic pathway key enzyme FOLR1, DHFR, SHMT, TS gene in nasopharyngeal resistant strains CNE-1/Taxol and HNE-2/Taxol expression found FOLR1, DHFR and SHMT in resistant strains CNE-1/Taxol, HNE-2/Taxol expression was significantly higher than their corresponding parental cell CNE-1 and HNE-2, prompted some of the key folate metabolic pathway enzyme changes may be associated with resistance to paclitaxel chemotherapy in nasopharyngeal carcinoma Drug relevant. 3.FOLR1 in normal nasopharyngeal tissues without expression, whereas in nasopharyngeal carcinoma had a lower rate of positive expression, the positive cells ranged from 0-42%, with an average (23.85 ± 13.89)%, with various clinical staging significant correlation (r = 0.9345, p <0.01), early tumor-positive rate is low, but positive rate of advanced tumors, indicating the occurrence of nasopharyngeal carcinoma and developments. Conclusions: 1. Nasopharyngeal carcinoma cell line resistant to the growth compared to the parental cell growth more dependent on folic acid; 2. Folate metabolism genes FOLR1, DHFR and SHMT with nasopharyngeal carcinoma cells resistant to paclitaxel relevant; 3.FOLR1 gene may become a target molecule treatment of nasopharyngeal carcinoma.

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CLC: > Medicine, health > Oncology > Department of Otolaryngology tumor > Pharyngeal tumors
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