Study Of The Influences Of Retinoic Acid And Taxol On Telomerase Activity Of Lung Cancer Cells And Its Antitumor Effect

Lung cancer is one of the most common malignant tumors in the world andits morbility and mortality are the highest among the human ma1ignant tumors inmany countries. It is we1l Anown that the etiology and pathogenesis of lungcancer is still not clear at tlie present tAne. SUrgery is the first choice fOr thetretheent of non-small cell lung cancer. Howevef, the prognosis of most patientswith lung cancer is poof, even in the cases underwent the curative radicaloperation, therefore, cotubined therapy is still a major treatffient of lung cancef,bllt there are many toxicity and side effeGts in combined theraPy. A lot ofmedical exPerts still look fOr a target of tumor treament, which is not present innormal c0lls but is present in cancer cells. Finally, the more and more attentionhas been lbcused on the relationship between cancer and telomerase. Telomerasehas become a hot point of medical research. ~Telomere play an driportant role in chromosome stability. Telomeraseactivity is required for cell immortality. At present, many artiGles have reportedthe close relationship betWeen activ8tion of telomerase and.Inalignant tumors.Telomerase activation in tumor cell is eXtremely prevalent. TherefOre telomerasemay be the marker of common tumor, it may be a universal target fOr cancertheraPy. The tf eatments of inhibiting telomerase will be the weakest toxic andside for cancer theraPyRetinoic AGid (KA) is one of the most classic cell differcntiation induceL Itmigh induce differentiation HL-60 cell line and Golon carcinoma cell linefollowing telomerase activity inhibited. Taxol has been regarded as one,D f themost useful drug fOr cancer treatffient and the first choice of the chemotheraPyof 1ung cancer. It might inhibit growth of cancer cell, but can Ilot i11l1ibittelomerase activity expressing in esophageal cancer and nasopharyngeal cancer. -.'ThQrQ is no report concerning the effects of RA combined with Taxol on the4ll jgroWth in both cell culture of luflg cancer cell line and the patients with lUIlgcancer Furthermore, there is no report conceming the effec13 of RA combinedwith Taxol on telomerase activity of lung cancer in vivo and y1itro.Objcctive RA and Taxol were included in this study to investigate f"l.The influence of RA or/and Taxol on telomerase activity of 1ung cancercell in vitro and in vivo.2.The influence of RA or/and Taxol on cell growth activity of luflg cancerce1l in vitro. -3.The influence of RA or/and Taxol on the growth of xenografts of lungcancer in nude mice.4.The mechanism of antitumor of RA odrid Taxol and the possibility ofthe aPp1ication of RA combined with Taxol in the tfeatfllent of patientswith 1ung canceLMcthod:l.The detection of IC,, of RA and Taxol on lung cancer cclls in vitro(MTTassay)A549 lung cancer cells were cultured with the control(culture medium) andtWo drugs at different concentrations fOr l,3and 5 days. The absorbance valueswere measured at 595nm and 630nm dual wave length. The cell activity and thepercelltage of cell inhibition were caculated to find out lC,., of RA and 'Ihxol atthe 1st, 3rd and 5th day respectively.2.The influences of RA and Taxol on lung cancer cells in vitr )According to the lC,., of RA and Taxol detected by MTT assay at the 3rdday 40umol/L RA, 20tunol/L Taxol, 40umol/L RA combined with 20umol/LTaxol were used to deal with lung cancer cells respectively Cells were collectedat the 3rd day of cultllre fOr the assay of telomerase activity. 1n the meanwhile,the cell activity and the percentage of cell inhibition were li.easured by MTT",assay.5J3.Tlie influences of RA and Taxol on subcutaneous xenografts of lung cancer innude mice40 male Bal b/c nude mice(aged 6-8 weeks and weighted about 20g)bearing subcutaneous xenograIls were randomly dividq;l into 5 'groups.Physiological saline, solvent, 40mg/kg ax, 36mg/kg Taxol, and 40mg/kg RAcombine with 36mg/kg Taxol were injected intraPeriton...