The invention provides application of E2F1 protein in preparation of a medicine for diagnosing and treating osteosarcoma, and application of the E2F1 protein in preparation of a product for treating osteosarcoma by virtue of differentiation therapy. The E2F1 protein is characterized in that the amino acid sequence is as shown in SEQ ID NO: 1. The experiment result shows that the expression of the E2F1 protein in an osteosarcoma tissue is obviously higher than that in a para-carcinoma tissue and is closely related to the differentiated degree of osteosarcoma. Therefore, E2F1 protein can be used as specific tag protein for diagnosing and treating osteosarcoma by virtue of the differentiation therapy; the diagnosis and treatment of osteosarcoma can be performed more accurately and quickly. The E2F1 protein can be used for providing a new treatment target and a new effective medicine for treating osteosarcoma.

Application of E2F1 protein in preparation of medicine for diagnosing and treating osteosarcoma

A novel VP-16 derivative, 4β-[N -(4‴-acetyloxyl-phenyl-1‴-carbonyl)-4″-aminoanilino]-4′-O-demethyl-4desoxypodophyllotoxin (GL3), displayed a wide range of cytotoxicity in a panel of human tumor cell lines, with half-maximal inhibitory concentration (IC50) values ranging from 0.82 to 4.88 μM, much less than that of VP-16 (4.18–39.43 μM). Importantly, GL3 induces more significant apoptosis and cell cycle arrest than VP-16. The molecular and cellular machinery studies showed that GL3 functions as a topoisomerase II (Top 2) poison through direct binding to the enzyme, and the advanced cell-killing activities of GL3 were ascribed to its potent effects on trapping Top 2–DNA cleavage complex, Moreover, GL3-triggered DNA double-strand breaks and apoptotic cell death were in a Top 2– dependent manner, because the catalytic inhibitor aclarubicin attenuated these biologic consequences caused by Top 2 poisoning in GL3-treated cells. Taken together, among a series of 4β-anilino-4′-O-demethyl-4-desoxypodophyllotoxin analog, GL3 stood out by its improved anticancer activity and well-defined Top 2 poisoning mechanisms, which merited the potential value of GL3 as an anticancer lead compound/drug candidate deserving further development.

Analog, Traps Topoisomerase II Cleavage Complexes and Exerts Anticancer Activities 1

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Application of E2F1 protein in preparation of medicine for diagnosing and treating osteosarcoma

Analog, Traps Topoisomerase II Cleavage Complexes and Exerts Anticancer Activities 1