Novel Mechanism of N-Solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine in Potentiation of Antitumor Drug Action on Multidrug-resistant and Sensitive Chinese Hamster Cells

The mechanism of the synthetic isopremoid N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediantine (SDB-ethylenediamine) in potentiating antitumor drug action against multidrug-resistant cells was comparatively studied with other potentiators such as verapamil and cepharanthine. SDB-ethylenediamine increased the accumulation of [³H]daunorubicin (DNR) in Chinese hamster V79 (V79/S) and its multidrug-resistant mutant (V79/ADM) cells. Even after SDB-ethylenediamine was removed from the medium, its effect continued. But when verapamil was removed from the medium, its effect disappeared immediately. Unlike verapamil and cepharanthine, SDB-ethylenediamine did not greatly inhibit the efflux of [³H]DNR from V79/ADM, the binding of [³H]vinblastine to membrane vesicles of V79/ADM, or the binding of [³H]azidopine to P-glycoprotein in the cytoplasmic membrane of V79/ADM. It did stimulate the influx of [³H]DNR into the ATP-depleted cells of V79/S and V79/ADM. Thus, SDB-ethylenediamine uniquely potentiates antitumor drugs. The increased intracellular accumulation of antitumor drugs in the presence of SDB-ethylenediamine is due not only to the inhibition of active efflux but also to the stimulation of the influx of antitumor drugs.     

Methylation of RASSF1A and CDH13 Genes in Individualized Chemotherapy for Patients with Non-small Cell Lung Cancer

Background: This study aimed to evaluate the methylation of RASSF1A and CDH13 gene promoter regions as a marker for monitoring chemotherapeutic efficacy with personalized medicine for patients with NSCLC, in the hope of providing a new direction for NSCLC individualized chemotherapy. Materials and Methods: 42NSCLC patients and 40 healthy controls were included. Patient blood samples were collected in the whole process of chemotherapy. Methylation of RASSF1A and CDH13 gene promoter regions was detected by the methylation specific polymerase chain reaction (MSP). Results: The rate of RASSF1A and CDH13 gene methylation in 42 cases of NSCLC patients was significantly higher than in 40 healthy controls (52.4% to 0.0%, 54.8% to 0.0%, p<0.05). After the chemotherapy, the hyper-methylation of RASSF1A and CDH13 genes in PR group and SD group decreased significantly (p<0.05), and was significantly different from that in PD group (p<0.05), but not as compared with healthy controls (P>0.05). With chemotherapy, RASSF1A and CDH13 promoter region methylation rate in 42 cases of patients showed a declining trend. Conclusions: The methylation level of RASSF1A and CDH13 gene promoter region can reflect drug sensitivity of tumors to individualized treatment.