Overexpression and Small Molecule-Triggered Downregulation of CIP2A in Lung Cancer

Abstract

BackgroundLung cancer is the leading cause of cancer deaths worldwide, with a five-year overall survival rate of only 15%. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein inhibiting PP2A in many human malignancies. However, whether CIP2A can be a new drug target for lung cancer is largely unclear.Methodology/Principal FindingsNormal and malignant lung tissues were derived from 60 lung cancer patients from southern China. RT-PCR, Western blotting and immunohistochemistry were used to evaluate the expression of CIP2A. We found that among the 60 patients, CIP2A was undetectable or very low in paratumor normal tissues, but was dramatically elevated in tumor samples in 38 (63.3%) patients. CIP2A overexpression was associated with cigarette smoking. Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. Intriguingly, we found a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells.Conclusions/SignificanceOur findings strongly indicate that CIP2A could be an effective target for lung cancer drug development, and the therapeutic potentials of CIP2A-targeting agents warrant further investigation.

Expression of cancerous inhibitor of protein phosphatase 2A in human triple negative breast cancer correlates with tumor survival, invasion and autophagy

“…CIP2A is a widespread oncogenic factor in human neoplasms (4)(5)(6)(7)(8)(9)3). Similar to the Ras oncogene, CIP2A is required for anchorage-independent cell growth and malignant transformation of human cells (4).…”

“…And 48 h transfection, the cells were harvested for western blot, cell viability, soft-agar colony formation assay, invasion assay and wound healing assay, as previously described (5,17).…”

“…Previous studies have shown that CIP2A serves a critical role in the progression of several cancer types, including head and neck squamous cell carcinoma, oral squamous cell carcinoma, oesophageal squamous cell carcinoma, colon, gastric, breast, prostate, tongue, lung, cervical cancer and acute myeloid leukaemia (3)(4)(5)(6)(7)(8)(9). In 2009, Côme et al (10) demonstrated that CIP2A is associated with clinical aggressivity in human breast cancer and promotes the malignant growth of breast cancer cells (10).…”

Alantolactone pyrazoline analogue inhibits cancer cell proliferation and induces apoptosis in non-small cell lung carcinoma cells

“…After 1 week, plates were stained with 0.5% gentian violet and the colonies were counted under light microscope (Ma et al, 2011).…”

Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition

“…A natural product, rabdocoetsin B, has been reported to inhibit CIP2A level and reduce cancer cell proliferation [7]. Although rabdocoetsin B shows CIP2A inhibition activity, the pure compound is not easy to obtain and purify.…”