Study of The Improvement of Docetaxel-Induced adverse Side Effects by Fungal Immunomodulatory Proteins

• Main Authors: Ting-Yi Hou, 侯婷譯
• Other Authors: Jiunn-Liang Ko
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/94190937091165475935

碩士 === 中山醫學大學 === 醫學研究所 === 102 === Docetaxel (TaxotereR) is usually applied in routine chemotherapy. However, the most common side effects of Docetaxel is myelosuppression, include neutropenia and anemia. Fungal Immunomodulatory Proteins of Flammulina velutipes and Ganoderma tsugaeare were called FIP-fve and FIP-gts, respectively. In previous study, both FIP-fve and FIP-gts have immunomodulatory and anti-cancer ability. This study is aimed to investigate the protective function of FIP-fve and FIP-gts on docetaxel-induced adverse side effects. In animal model, complete blood count (Control v Docetaxel) reveals neutropenia (WBC：6.29 ± 1.19 × 103/μL v 3.40 ± 0.74 × 103/μL) and anemia (RBC：9.19 ± 0.52 × 106/μL v 8.06 ± 0.43 × 106/μL). Moreover, FIP-gts but not FIP-fve can reverse docetaxel-induced neutropenia (Docetaxel v Docetaxel combined with FIP-gts，3.40 ± 0.74 × 103/μL v 5.81 ± 1.64 × 103/μL). As compared to Control group (570.38 ± 68.66 μm), histological sections of intestine shows that villous length was decrease in Docetaxel group (365.85 ± 19.21 μm), Docetaxel combined with FIP-fve (474.65 ± 6.8 μm) and Docetaxel combined with FIP-fve (506.60 ± 17.87 μm)), respectively. Consequences, FIP-fve and FIP-gts significantly decreased docetaxel-induced intestine damage. Moreover, numbers of adipocyte (% of control) was significantly increased in Docetaxel group (275.27 ± 45.31%) as compared to Control group (100 ± 22.04%) in bone marrow. FIP-fve (154.84 ± 22.35%) and FIP-gts (138.71 ± 12.35%) can decrease docetaxel-induced adipocyte in bone marrow. Quantification of trabecular bone (Control v Docetaxel) percent bone volume (21.82 ± 1.10% v 11.35 ± 3.32%), trabecular number (3.12 ± 0.26 mm-1 v 1.66 ± 0.45 mm-1), bone surface density (12.20 ± 0.99 mm-1 v 6.82 ± 1.67 mm-1), and trabecular separation (0.21 ± 0.02 mm v 0.379 ± 0.109 mm) analyzed by on 3D micro-CT analysis. This is reason that Docetaxel induced bone damage and increase osteoporosis risk. Moreover FIP-fve and FIP-gts significantly reversed docetaxel-decreased percent bone volume, trabecular number and bone surface density. On the enzyme-linked immunosorbent assay (ELISA), total plasma G-CSF concentration was significantly increased in Docetaxel + FIP-gts group (145.14 ± 76.74 ρg/mL) as compared to Docetaxel group (72.88 ± 39.19 ρg/mL). Both of FIP-fve and FIP-gts can stimulate G-CSF mRNA expression in human peripheral blood mononuclear cells (hPBMCs) by RT-PCR and inhibit A549 cell survival by MTT assay. Both of FIP-fve and FIP-gts reduce the mRNA expression of monocyte chemotactic protein-1 (MCP-1), which promotes lung cancer-induced bone resorptive lesions in A549 lung cancer cells by RT-PCR and ELISA. This is the first study to reveal the novel function of FIP-fve and FIP-gts in mitigating docetaxel-induced adverse side effects. Therefore, we suggest that FIP-fve and FIP-gts may be potential adjuvants of docetaxel.