91猫先生

研究方向及研究室特色：

本研究室的主要方向為探索癌症转移及恶病质的分子机制，并开发有效对抗肿瘤生长和进展的天然物或新型合成药物。研究成果将為癌症转移、恶病质分子机转和癌症治疗策略提供新见解。

1. 探讨癌症转移/恶病质的分子机制

头颈癌是世界第六大最常见的癌症。每年全球每年有60万新诊断的头颈癌病例。过去20年流行病学研究表明， 45岁以下年轻头颈癌患者（尤其是口腔鳞状细胞癌）的整体发生率正在稳定增长。因此，瞭解头颈癌进展的分子机转是开发治疗策略的基础。我们过去研究显示头颈癌细胞中IFIT2 (interferon induced protein with tetratricopeptide repeats 2) 蛋白缺失可以增强上皮-间质转化（epithelial-mesenchymal transition），迁移 (migration)，侵袭 (invasion)，血管生成 (angiogenesis) 和转移 (metastasis)，阐明IFIT2抑制癌症转移之作用。近来实验结果发现转移性IFIT2蛋白缺失头颈癌肿瘤会造成小鼠表现恶病质症状。恶病质是癌症患者中最致命的影响之一。头颈癌病患中发生恶病质的频率相当高（60-80％）。然而，其详细分子机制了解甚少。因此，我们未来目标為探究头颈癌症转移、恶病质的分子机转。

2. 开发具有抗肿瘤潜力的天然产物或新型合成药物

过去，我们也测试天然物，如木蝴蝶素A (oroxylin A)、牛樟芝 (Antrodia cinnamomea; AC) 萃取物，及新合成喹唑啉酮衍生物 (quinazolinone derivatives) 对抗肿瘤的治疗潜力。為了检测天然物长期服用的抗肿瘤潜力，我们建立了体外长期暴露模型并证明了长期木蝴蝶素A暴露可抑制口腔癌细胞中CCL2讯息传递路径进而削减癌细胞的迁移。此外，亦证实新型牛樟芝萃取物在结肠直肠癌细胞的抗肿瘤机制。目前则是检测新型DNA双功能烷基化剂和新型喹唑啉衍生物之抗肿瘤作用。未来将会试验更多对肿瘤生长和进展有治疗潜力的天然物或新型合成化学製剂。

论文发表：

1. Lai KC*, Hong ZX, Hsieh JG, Lee HJ, Yang MH, Hsieh CH, Yang CH, Chen YR. IFIT2-depleted metastatic oral squamous cell carcinoma cells induce muscle atrophy and cancer cachexia in mice. Journal of Cachexia, Sarcopenia and Muscle. Feb., 2022;Journal of Cachexia, Sarcopenia and Muscle 2022; 13: 1314–1328
2. Lai KC, Chia YT, Yih LH, Lu YL, Chang ST, Hong ZX, Chen TL, Hour MJ. Antitumor effects of the novel quinazolinone Holu-12: Induction of mitotic arrest and apoptosis in human oral squamous cell carcinoma CAL27 cells. Anticancer Research. Jan., 2021, 41 (1): 259-268. 
3. Regmi P, Lai KC, Liu CJ, Lee TC. SAHA overcomes 5-FU resistance in IFIT2-depleted oral squamous cell carcinoma cells. Cancers (Basel). Nov., 2020, 12 (12): 3527.doi: 10.3390/cancers 12123527
4. Patel AS, Jain V, Rao VN, Lin YW, Shah A, Lai KC, Su TL, Lee TC. Design, synthesis and antitumour evaluation of pyrrolo[1,2-f]-phenanthridine and dibenzo[f,h]pyrrolo [1,2-b]isoquinoline derivatives. European Journal of Medicinal Chemistry, Sep., 2020, 202:112516.
5. Lin TJ, Lai KC, Lee AS, Chang CH, Liu CL and Chung CH. Novel antrodia cinnamomea extract reduced cancer stem-like phenotype changes and resensitized KRAS-mutant colorectal cancer via a microRNA-27a pathway. Cancers, Oct.,2019, 11(11): 1657. doi: 10.3390/cancers 11111657
6. Ku WT, Tung JJ, Tony JF Lee, Lai KC*. Long-term exposure to oroxylin A inhibits metastasis by suppressing CCL2 in oral squamous cell carcinoma cells. Cancers (Basel).Mar., 2019, 11 (3): 353. doi: 10.3390/cancers 1103035
7. Chu CH, Chang SC, Wang HH, Yang SH, Lai KC*, Lee TC*. Prognostic values of EPDR1 hypermethylation and its inhibitory function on tumor invasion in colorectal cancer. Cancers (Basel). Oct., 2018, 10 (10): 393 doi: 10.3390/cancers 10100393
8. Lai KC, Liu CJ, Lin TJ, Mar AC, Wang HH, Chen CW, Hong ZX, Lee TC. Blocking TNF-α inhibits angiogenesis and growth of IFIT2-depleted metastatic oral squamous cell carcinoma cells. Cancer Letters. Jan., 2016, 370 (2): 207-215.
9. Chen YJ, Lai KC, Kuo HH, Chow LP, Yih LH, Lee TC. HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide. Archives of Toxicology, Sep., 2014, 88 (9):1711-1723.
10. Lai KC, Liu CJ, Chang CK, Lee TC. Depleting IFIT2 mediates atypical PKC signaling to enhance the migration and metastatic activity of oral squamous cell carcinoma cells. Oncogene, Aug., 2013, 32 (32): 3686-3697.
11. Hung KF, Lai KC, Liu TY, Liu CJ, Lee TC, Lo JF. Asb6 upregulation by areca nut extracts is associated with betel quid-induced oral carcinogenesis. Oral Oncology,Jun., 2009, 45 (6):543-548.
12. Lai KC, Chang KW, Liu CJ, Kao SY, Lee TC. IFN-induced protein with tetratricopeptide repeats 2 inhibits migration activity and increases survival of oral squamous cell carcinoma. Molecular Cancer Research, Sep., 2008, 6 (9):1431-1439.
13. Lai KC, Lee TC. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutation Research- Fundamental and Molecular Mechanisms of Mutagenesis, Jul., 2006, 599 (1-2): 66-75.

获奖纪录:

2016 荣获台湾药理学会『104年度杜聪明博士年轻学者奖』

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