The Cytotoxic Molecule Ansamitocin P-3 Suppresses Cell Proliferation and Tumor Growth in Lung Carcinoma

Lung cancer, mainly including small cell lung cancer (SCLC) and non-small lung cancer (non-SCLC, nSCLC), is a malignant and aggressive one and the leading cause of cancer-related death worldwide. Patients at late stages of lung cancers are usually treated with radiotherapy and chemotherapy. These traditional therapies displayed very limited benefits, with a poor five-year survival rate. The receptor-targeting therapy is becoming a new hot topic. Our previous studies demonstrated the receptor-targeting drug conjugates could enhance the anti-tumor efficacy of the free molecules via linking them to peptide vehicles. Presently, three chemical molecules camptothecin, AP-3 and colchicine were pre-tested for their cytotoxic activities in SCLC A549 cells and non-SCLC NCI-H69 cells. All these molecules displayed their potent effects on cell proliferation and cell apoptosis in both. Especially, AP-3 was extremely more potent than the other two. Our further in-vivo assay showed that AP-3 suppressed NCI-H69 tumor growth, but had a limited ability. A new strategy may be needed for AP-3 in SCLC treatment. Meanwhile, We found that somatostatin receptor type II (SSTR2) was highly expressed in SCLC cells, not non-SCLC cells. These findings may provide a golden opportunity to develop a SSTR2-targeting AP-3 somatostatin conjugate for SCLC treatments.

Author(s):

Jinlei Ye, Shilei Wang, Ying Chen, Jie Tang, Zhilei Cui, Qiping Zheng and Lichun Sun

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