Use Of Olanzapine For Prevention Of Nausea And Vomiting,and Experiments About Inhibition Of Lung Cancer Cell

Objective In this study,we explored the relief effection of olanzapine on chemotherapyinduced nausea and vomiting(CINV)in cancer patients.Furthermore,we investigated the inhibition of olanzapine for Epithelial-Mesenchymal Transition(EMT)in H1299 and A549 cell lines.Interestingly,olanzapine demoted the ability of invasion and migration in H1299 and A549 cell lines in vitro.Methods1.Collect cancer patients from the oncology department of the first affiliated hospital of dalian medical university for 74 patients.We retrospectively analyse use of olanzapine for relief of nausea and vomiting.On the basis of 5-HT receptor inhibitors combined dexamethasome,we choose patients who did not get treatment of olanzapine in the first 1-4 cycles and take it in more than 2-4 cycles.According to a WHO recommend criteria about grade of antitumor drug toxicity and a simplified version of the assens insomnia scale,we evaluate CINV and sleep.The same chemotherapy regimen before and after olanzapine taking must be consistent.1.1 Record basic information(name,hospital number,sex and age);1.2 Observe the number of total nausea and vomiting(nausea,vomiting,hiccups,and vomiting)in the first and fifth days of the chemotherapy;1.3 Observe the overall condition,sleep,ECOG scores,and NRS scores.2.Olanzapine inhibited of lung cancer cells,and selected lung adenocarcinoma cells H1299,pneumosquamous cell A549,and normal pulmonary fibrocytuses,HLF2.1 Cell clone formation experiment: lung adenocarcinoma cancer cell H1299,lung squamous cancer cells A549 were diluted(103 / ml),respectively.Gradient concentrations of olanzapine(25,50,100 ?M)incubated for 7 days.Use photoshop to count number of cell cloning,and observe cells form at the 7th day;2.2 Thiazole blue dye: an enzyme that monitors half concentration of olanzapine against H1299,A549,and HLF;2.3 Serum-free microsphere suspension cell culture: limited dilution of H1299,A549 to 103 / ml,then trained for 10 days.Finally,count and measure H1299,A549 the number and diameter of microspheres under inverted microscope;The wound healing assay: taking picture of H1299,A549 cells in the 0th,12 th,36th,and 72 th hour under a microscope and measure the distance of cells scraped;Invasive test transwell assay: after 12 hours,the number of A549 invased and penetrated the basement membrane was recorded;2.4 Nude mice(BALB/C Nude)lung cancer metastasis model: from 6 Nude mice,randomly selected 3 and give them sterile water containing 0.05 mg/ml olanzapine for 7 days.In the 7th day,all the Nude mice inoculated lung squamous carcinoma A549 cells through tail intravenous.Thirty days after inoculation,Nude mice were anesthesia executed and anatomy.Then observe and statistics the number and size of A549 cells in lung metastases.Results:1.Olanzapine reduced CINV incidence,improved sleep,and reduced ECOG scores and NRS scores.1.1 CINV incidence of combined olanzapine or not is 86.5% and 67.6%respectively(? 2 = 3.742,P = 0.048),which is statistically different.;1.2 The incidence of sleep disorder is 12.3% and 33.4% respectively(? 2 =4.163,P = 0.044),which is statistically different;the proportion of ECOG score 1 or less is 94.6% and 83.8%,respectively(? 2= 2.242,P = 2.242),which is no statistically different;The proportion of NRS = 0 is 89.2% and 78.4%,respectively(? 2 = 1.591,P= 1.591),which is no statistically different.2.Olanzapine inhibits metastases of lung adenocarcinoma cell line H1299,Pneumoid cell A549,and promotes A549 differentiation.2.1 Ability of 25 ?M olanzapine treatment H1299 and A549 colony-forming reduces to 75.19 % ± 1.42 %,72.27 % ± 2.38 %(P < 0.01);The 50 ?M was reduced to 61.4 % ± 5.32 %,29.13 % ± 3.17 %(P < 0.001);The 100?M was reduced to 15.04 % ± 3.54 %,10.64 % ± 2.38 %(P < 0.001),which is statistically different,significantly.2.2 Olanzapine specifically inhibited H1299,A549,compared to HLF.Half of inhibition concentration(IC50)of HLF,H1299,and A549 are 603.34±16.1 ?M,142.85±8.4 ?M,129±8.6 ?M(P < 0.01),which is statistically different.2.3 The number of microspheres in H1299 and A549 was reduced to 20.04 % ±7.54 %,18.59 % ± 4.87 %(P < 0.001);The migration distance was reduced to 40.24 % ± 5.12 %,46.7 % ± 52.2 %(P < 0.01);The number of A549 penetrated the basement membrane was reduced to 34.2 % ± 5.64 %(P <0.01),which is statistically different,significantly.2.4 Mice of olanzapine group was reduced to 56.4 % ± 12.2 %(P < 0.05),which is statistically different;The number was reduced to 34.2 % ± 13.1 %(P< 0.01),which is statistically different.Conclusion1?Olanzapine reduces the incidence of CINV,which is statistically different,(P < 0.05);Olanzapine improves patient's sleep condition,which is statistically different,(P < 0.05);Olanzapine decreases patient's ECOG scores and NRS scores,which is no statistically different,(P > 0.05).2?Olanzapine inhibits the proliferation of pulmonary adenocarcinoma H1299 and pneumoid cell A549,which is statistically different,significantly,(P <0.01);Olanzapine inhibits H1299 and A549 invasion and penetration of the basement membrane,which is statistically different,significantly,(P < 0.01);Olanzapine decreases H1299 and A549 migration distance,which is statistically different,significantly,(P < 0.01);Olanzapine reduces the number and size of metastases in the lung of the mice,which is statistically different,significantly,(P < 0.01).