Establishment Of A Paclitaxel-Resistant Human Lung Adenocarcinoma Cell Line & Studies On MDR-reversing Activity Of New Taxanes And The Mechanisms Of Action

Multidrug resistance(MDR) is one of the major obstacles in successful chemotherapy of cancer. The investigation of resistant mechanism developed by tumor and the search for novel and potent reversal agents of MDR is the focus of the development of new chemotherapeutic agents. In the Part I of this paper, we described the establishment of a paclitaxel-resistant human non-small cell lung cancer (NSCLC)-lung adenocarcinoma cell line, A549/Taxol, by continuous stepwise exposure of NSCLC A549 to paclitaxol for 15 months, the identification of biological characteristics and explored the possible mechanism of resistance of A549/Taxol. In the Part II of this paper, three Taxinine derivatives, Sy1219, Sy1220 and Sy1221, were studied for the antitumor action, inducing the differentiation of mouse melanoma cell B16, B16-BL6, inhibition of angiogenesis, reversal action of MDR in vitro and in vivo and the possible mechanism of MDR-reversal by Syl220.1. Establishment of a Paclitaxel-Resistant Human Lung Adenocarcinoma Cell LineTo establish MDR cell line in vitro is an important method to study the MDR mechanism and look for now reversal agents of MDR. A549/Taxol, a paclitaxel resistant subline of human NSCLC cells A549, was selected by continuous exposure to increasing paclitaxel concentration from 8.74×10^-13 mol/L to 2×10^-8 mol/L. The IC₅₀ values of...