Liao Chien-Huang, Hsiao Yi-Min, Lin Ching-Hsiung, Yeh Chin-Shui, Wang James Chun-Huan, Ni Chia-Hung, Hsu Chung-Ping, Ko Jiunn-Liang
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Food Chem Toxicol. 2008 May;46(5):1851-9. doi: 10.1016/j.fct.2008.01.044. Epub 2008 Feb 2.
Purified recombinant fungal immunomodulatory protein from Ganoderma tsugae (reFIP-gts) has anti-telomerase effects in human lung adenocarcinoma A549 cells. However, how reFIP-gts affects cancer cell fates remains unclear. Here, we demonstrated that reFIP-gts-treated lung cancer cells are arrested at G1 phase by flow cytometry and possess morphological phenotype consistent with cellular senescence. The senescent nature of these cells was supported by positive staining for senescence-associated beta-galactosidase activity and increased lysosomal content in A549 and CaLu-1 lung cancer cells. Arrest of cells at G1 appears to be the key means through which reFIP-gts induces premature cellular senescence in A549 cells. Finally, reFIP-gts- treated A549 cells grew more slowly and formed significantly fewer cell colonies in soft agar than untreated A549 cells. In an in vivo mouse model, A549 cells treated with reFIP-gts grew significantly slower than cells treated with PBS alone, confirming that lung tumor can be inhibited by reFIP-gts. The use of reFIP-gts may be a powerful new strategy for chemoprevention and antineoplastic therapy.
从松杉灵芝中纯化得到的重组真菌免疫调节蛋白（reFIP-gts）对人肺腺癌A549细胞具有抗端粒酶作用。然而，reFIP-gts如何影响癌细胞命运仍不清楚。在此，我们通过流式细胞术证明，经reFIP-gts处理的肺癌细胞停滞于G1期，且具有与细胞衰老一致的形态学表型。衰老相关β-半乳糖苷酶活性的阳性染色以及A549和CaLu-1肺癌细胞中溶酶体含量的增加支持了这些细胞的衰老特性。细胞在G1期停滞似乎是reFIP-gts诱导A549细胞过早细胞衰老的关键途径。最后，经reFIP-gts处理的A549细胞生长比未处理的A549细胞更慢，并且在软琼脂中形成的细胞集落明显更少。在体内小鼠模型中，经reFIP-gts处理的A549细胞生长明显比单独用PBS处理的细胞更慢，证实reFIP-gts可抑制肺肿瘤。使用reFIP-gts可能是一种强大的化学预防和抗肿瘤治疗新策略。
