ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the underlying mechanism of Jianpi Jiedu Recipe (, JJR) in the reversion of multidrug resistance concerning colorectal cancer in vitro and in vivo.</p><p><b>METHODS</b>Mice were treated orally with JJR at a daily 4.25 g/(kg·day) or injected with vinblastine (VCR) 2.5 mg/(kg·day) for 3 weeks after having been inoculated with HCT8/V cells; tumor tissues were assayed by hematoxylin and eosin staining. Firstly, the effects of JJR on the expression of cyclooxygenase-2 (COX-2) were tested by real-time polymerase chain reaction (PCR) technique and COX-2 gene silenced by siRNA. Secondly, the variation of intracellular concentration of oxaliplatin (L-OHP) was evaluated by the inductively coupled plasma mass spectroscopy (ICPMS) in HCT8/V and its COX-2 siRNA cells; the concentration of JJR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8/V cells was evaluated by the MTT assay. Thirdly, real-time quantitative PCR and Western blot analysis were used to detect the multidrug resistance gene 1 (MDR1) mRNA and P-gp expression.</p><p><b>RESULTS</b>JJR had an inhibitory effect on the growth of tumors in vivo, and it, in combination with chemotherapeutic drugs, could reverse the drug-resistance of HCT8/V cells and increase the sensitivity of HCT8/V cells to VCR, DDP, 5-Fu, and THP. ICP-MS results showed that JJR could increase the concentration of drugs in HCT8/V cells (P<0.01). Furthermore, it was shown that JJR could reverse drug resistance of colorectal cancer cells by decreasing MDR1 expression and P-gp level via downregulation of COX-2, which has been represented as one of the major mechanisms that contributes to the MDR phenotype (P<0.01).</p><p><b>CONCLUSION</b>JJR reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2 in MDR1/P-gp-mediated MDR colorectal cancer after chemotherapy.</p>
Subject(s)
Animals , Female , Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms , Drug Therapy , Pathology , Cyclooxygenase 2 , Genetics , Metabolism , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Green Fluorescent Proteins , Metabolism , Intracellular Space , Metabolism , Mice, Inbred BALB C , Organoplatinum Compounds , Metabolism , RNA, Small Interfering , Metabolism , Signal Transduction , Vinblastine , Pharmacology , Therapeutic Uses , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To determine the feasibility on the left ventricular systolic synchronism and cardiac function evaluation in patients with permanent cardiac pacing by real-time three-dimensional echocardiography.</p><p><b>METHODS</b>Fifteen patients with sick sinus syndrome post dual-chamber pacemaker implantation were enrolled in this study. Pacemakers were programmed to AAI, DDD, and VVI respectively. After pacing for 5 minutes in each mode, participants were examined with real-time three-dimensional echocardiography. Images in different pacing modes were obtained and analyzed by the off-line Qlab 4.2 software. Parameters including global and 17-segmental volume-time curves (VTCs), dispersion of time to minimal regional volume for 16, 12, and 6 left ventricular segments (Tmsv16-s, Tmsv12-s, Tmsv6-s), and maximal difference of time to minimal regional volume for l6, 12 and 6 left ventricular segments (Tmsv16-dif, Tmsv12-dif, Tmsv6-dif), end diastolic volume (EDV), end systolic volume (ESV), left ventricular ejection fraction (LVEF) were measured respectively. Parameters of peak filling rate (PFR), regional end diastolic volume (rEDV), regional end systolic volume (rESV), and regional ejection fraction (rEF) were also calculated.</p><p><b>RESULTS</b>Left ventricular systolic synchronism as reflected by VTCs, Tmsv16-s, Tmsv12-s, Tmsv6-s, Tmsv16-dif, Tmsv12-dif and Tmsv6-dif as well as parameters reflecting ventricular function, i.e., LVEF, PFR were significantly better in AAI mode than in DDD and VVI models (all P < 0.05). All above indexes were similar between DDD and VVI models (all P > 0.05). rEFs of left inferior wall in base, septum in base and apex were significantly lower in DDD and VVI models compared that in AAI mode (P < 0.05).</p><p><b>CONCLUSION</b>Real-time three-dimensional echocardiography can objectively and accurately evaluate left ventricular systolic synchronism and cardiac function in patients with permanent cardiac pacing and AAI mode is superior to DDD and VVI models.</p>