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Antitumor effect of Chinese herb oridonin on human non-small cell lung cancer (NSCLC).
Developmental Therapeutics - Experimental Therapeutics
Session Type and Session Title:
This abstract will not be presented at the 2012 ASCO Annual Meeting but has been published in conjunction with the meeting.
J Clin Oncol 30, 2012 (suppl; abstr e13526)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Oridonin, a diterpenoid purified from the Chinese herb Rabdosia rubescens, has anti-inflammatory and potentially anti-tumor property. We aimed to study the antitumor effect of oridonin on a panel of human non-small cell lung cancer (NSCLC) cell lines. Methods: Human NSCLC cell lines with a wild-type EGFR gene and a RAS gene mutation were treated with escalating dose concentration of oridonin (from 2.5 to 50 µM). Antitumor effect was measured by 72-hr growth inhibition by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell morphology was observed under microscope. Ongoing experiments will identify potential drug target(s) by assessing changes in global gene expression. Results: Oridonin exhibited a dose-dependent and time-dependent cytotoxic effect on a panel of NSCLC cell lines. Table 1 summarizes the molecular and histological features of these NSCLC cells, and their cytotoxicity to oridinin, erlotinib and pemetrexed. In those NSCLC cells that were sensitive to oridonin, morphological changes were consistent with autophagy and apoptosis. Potential drug targets will be verified by RT-PCR and immunoblotting. Conclusions: Oridonin exerts a distinct cytotoxicity that is independent of the sensitivity of NSCLC cells to erlotinib or pemetrexed. Further mechanistic and animal studies are warranted to understand its anti-tumor property and toxicity profile in preclinical evaluation.
|Cell line||Cell type||EGFR gene||RAS mutation||p53 mutation||Erlotinib IC50
|1.50 ± 0.16||0.24 ± 0.04||31.45±7.60|
|R#2||adenocarcinoma||Wild-type||NRAS Q61K||Wild-type||>20||0.34 ± 0.06||24.76±3.17|
|H23||adenocarcinoma||Wild-type||KRAS G12C||M246I||>20||0.46 ± 0.08||25.72±1.17|
|A549||adenocarcinoma||Wild-type||KRAS G12S||Wild-type||>20||0.35 ± 0.06||79.48±28.20|