The concentration of gleevec to inhibit 50% cell growth ic50 was estimated to be around 23. Cisplatin was also found to cause ros generation and increase lipid peroxidation, which leads cells to the apoptotic pathway. We have also seen that gleevec can inhibit the growth of human 293 kidney cells, but at slightly higher concentration 4. Every two months, cell survival was analyzed by mtt assay. Inhibition of the cervical cancer growth by cidan and cisplatin. The a2780cp70 cell line was fold more resistant to cisplatin than a2780 cells. Covid19 is an emerging, rapidly evolving situation. Ratio of cisplatin ic50 to compound ic50 for mouse b16f10. Here, we have asked whether variations in the constitutive expression of earlygrowth response factor 1 egr1 predicted acute cytotoxicity and clonogenic cell death in vitro, induced by six different chemotherapics.
Role of autophagy in cisplatin resistance in ovarian cancer cells. Enhancement of cisplatin sensitivity of cisplatinresistant human. Cell apoptosis was examined by cytometry and hoechst33258 staining after treatment with cisplatin. Less than 30% of malignant gliomas respond to adjuvant chemotherapy.
Combinations of the treatments that induced growth inhibition higher than those of the same doses used alone p 0. Cisplatin binds covalently to cellular proteins and labels cells with compromised cell membranes to a much greater extent than live cells. To provide precise and unbiased ic50 measurements, we developed a novel technique that. Ratio of cisplatin ic50 to compound ic50 for human a431 cells. In hela cell line, the ic50 value of methanol extract of llf was16 1. The half maximal inhibitory concentration ic50 of cisplatin in hela and siha cells at 72 hours was. Iii study of gemcitabinecisplatin versus etoposidecisplatin in the treatment of. Platinum complexes with bioactive nitroxyl radicals. May 29, 2014 the platinum derivative cisdiamminedichloroplatinumii, best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck.
After 24h of these treatments, cells were trypsinized and spin at 2000 rpm for 3 minutes, then washed twice with cold pbs. Skov3 cells offers ic50 values ranging from 2 to 40. The increased sensitivity to cisplatin observed after adenoviral fhit gene transfer in h460 cells was reduced in bcl2 and bclx loverexpressing clones compared with h460 parental cells when measured using clonogenic assay. The corresponding ic50 values of cisplatin on cne2 and hne1 cells were 1. In the presence of 30 m dip, the ic 50 of cisplatin was reduced by 39% for both cell lines. In this study, t47d cells were treated with various concentrations of cisplatin 0, 3. Cidan and cisplatin reduced the viability of hela cells at 48 h to 43. Introduction inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of nonsmall cell lung cancer nsclc. Cetuximab and cisplatin show different combination effect in. Anderson cancer center, 1515 holcombe boulevard, houston, tx 770304009, usa cisplatin is one of the most potent antitumor agents. May 02, 2014 the development of cisplatin resistance results in treatment failure, but the underlying mechanisms are not fully understood. Cisplatin induces down regulation of bcl2 in t47d breast. The subline showed a collateral sensitivity to paclitaxel. Following the 48 and 72h hour treatments at 37c, cells were.
Generation and characterisation of cisplatinresistant non. Cell apoptosis was measured with flow cytometry and hoechst 33258 staining following cisplatin treatment. Apexbio cisplatininhibits dna synthesis,chemotherapy drug. Cisplatina resistant hela cells are resistant to apoptosis. P cisplatin activates sapkjnk, p38 kinase, and erk dose dependently in cisplatin sensitive hela cells, whereas cisplatin mediated activation of sapkjnk is significantly reduced in the cpr subline.
M, respectively p jul 23, 2015 hypoxia enhanced the cisplatin resistance of lung cancer cells. The doseresponse study showed that hepg2 cells were slightly more sensitive to cisplatin in undergoing apoptosis than hep3b cells, with apoptosis observed at a lower dose of cisplatin 4. Some experiments have found that cisplatin can inhibit protein expression in hela cells of cervical cancer cell lines, promote cell apoptosis significantly and inhibit the growth to achieve a. Inhibition of cyclin d1 expression by cyclin d1 shrnas in. In cochlear cells, cisplatin treatment results in the increase of caspases3 and 9 and causes the cochlear damage side effect 1. The inhibitory effect of cisplatin on hela cell growth was analyzed by the mtt assay. After 24h of incubation, cells were treated with ceo 125. Combination of cisplatin and cinnamon essential oil.
Doseresponse curves for hela, siha, vero, and 3t3 cell. Treatment with double agents in these two cell lines could achieve an additive cytotoxic effect compared with the single agent groups. A cisplatin resistant cell subline, helacddp cells, showed a 19fold resistance to cisplatin compared with the parent cells. Apoptosis is the main response of cells to chemotherapeutic agents including cisplatin. The enhanced inhibitory effect of different antitumor agents. The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosispromoting effects on hela cells p cells exposed to cisplatin free solvent 0. Here we show that the induction of autophagy plays an important role in cisplatin resistance in ovarian cancer cells. Cytotoxicity and antitumor effects of new ruthenium.
Pdf metformin enhances antiproliferative effect of cisplatin in. Tthe study of combination resulted that almost all the index combinations were ic50 cisplatin 18 ic50 elh. Cytotoxicity assays were performed on cells derived from fresh tumor explants of 18 human cases of malignant. Potential implications of grp58 expression and susceptibility. Cells viability was determined by using mtt assay as described in methods.
Inhibitory concentration ic50 of cisplatin and metformin was determined before. M, cisplatin sensitivity increased in both cell lines compared to cisplatin treatment alone. The ic50 of elh and cisplatin on hela cells were 227 gml and 17 m. In 2011, hela cells were used in tests of novel heptamethine dyes ir808 and other analogs which are currently. The effects of cisplatin on transcription of e6 were analyzed by rtpcr. Since the discovery of cisplatin more than 40 years ago and its clinical introduction in the 1970s an enormous amount of research has gone into elucidating the mechanism of action of cisplatin on tumor cells. Analysis and identification of novel molecules with antitumor activity is useful for. The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosispromoting effects on hela cells p cisplatin in skov3 cell line, and it varied from 2 to 40 um. Hela cells 1x104 cellswell were seeded in 96 wellplate and incubated for 24h, then treated with ceo 50500 gml or cisplatin 550 m. The effect of cisplatin on transcription of hpv e6 was analyzed by rtpcr and protein expression. Cisplatin and doxorubicin were added twice a week after reseeding. Students ttest was used as a cutoff for scoring hits. Cisplatin doseresponse curve of hela cells treated in suspension with 4 pgml cisplatin for one to 4 h under aerobic a or hypoxic a conditions.
Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Then, cell viability was assessed using mtt assay and ic50 was determined. The mechanism of cisplatininduced apoptosis in hela cells. The changing 50% inhibitory concentration ic50 of cisplatin. The half maximal inhibitory concentration ic 50 of cisplatin in hela and siha cells at 72 hours was. Preparation and cytotoxicity of cisplatincontaining liposomes. M figure 1, whereas the ic50 of cisplatin on a549 cells was estimated to be 6470. The timecourse study showed that dna fragmentation in hepg2 cells was detectable at 12 h after. A2780s cells were more susceptible to both cisplatin and carfilzomib while analyses of drug interactions between the two agents showed synergistic effects in all affected fractions of drugtreated a2780s and a2780cp cells ci0. Induction of cisplatin resistance in a2780 cell line cisplatin resistant a2780 cell lines were derived from original parental cell line by continuous exposure to stepwise increasing concentrations of cisplatin. With a novel cell biosensor chip system allowing continuous monitoring of respiration, glycolysis, and impedance we followed cisplatin treatment of different cancer cell lines in real. Hela cells were seeded at 5x105cellswell on six wells tissue culture plate. Meanwhile, the ic50 of thymoquinone in hela and siha cells was 29.
Cisplatinresistant cells in malignant pleural mesothelioma. When hela cells were irradiated in the presence of cisplatin under hypoxic conditions, the resulting c e d lo. Meanwhile, the ic 50 of thymoquinone in hela and siha cells was 29. Increased sensitivity to cisplatin in nonsmall cell lung. Cell death found in flow cytofluorimetry experiments was shown to be apoptotic. Methods an isogenic model of cisplatin resistance was generated in a panel of nsclc cell. Sensitivity to cisplatin in primary cell lines derived from.
Synthesis and cytotoxicity evaluation of novel asymmetrical mono. In addition, cisplatin induces apoptosis with the caspasedependent pathway. Table 1 ci value of administration of metformin and cisplatin in hela cells. Hela is an immortal cell line used in scientific research. When studied at their respective ic50 doses, drug accumulation rates were similar for the two cell lines. Jci acquired cisplatin resistance in human ovarian cancer. Invitro phytopharmacological and anticancer activity of loranthus. For the lung is the firstline to contact with the atmosphere, in which the oxygen content is 21%, so 21% o2 is commonly used as. However, cisplatin has been reported to cause drug resis tance and. An equitoxic dose ic50 of cisplatin produced dna fragmentation in hela cells but not in helacddp cells.
Induction of apoptosis by cisplatin and its effect on cell. After the transfection with the 2 most effective shrnas, the cisplatin ic50 decreased from 5. Cisplatin has a number of side effects that can limit its use. Platinum accumulation in both sensitive and resistant cell lines. To study the mechanism of apoptosis induced by cisplatin in vitro in hela cells cervical cancer cell line. Cell cycle analysis of hela and h1299 cells treated with cisplatin and complex 10d concentration ic50, 24 h. What is ic50 of cisplatin for hek cell line for a 24 hr study. However, marked sensitization to cisplatin was observed in terms of apoptosis. M, respectively p hela cells by cidan and cisplatin in dose and time dependent manner. Generation of cisplatinresistant ovarian cancer cell lines. Dipyridamole increases the cytotoxicity of cisplatin in human.
The effect of combined treatment of hela cells with cisplatin. To study the apoptosis induced by cisplatin in cervical cancer cell line hela and its mechanism, cell growth inhibition of cisplatin on hela cells was analyzed by mtt assay. Combination of cisplatin and cinnamon essential oil inhibits. Each plate included controls of untreated cells, cells treated with compounds or cisplatin only, and cells treated with a combination of both agents. Some scientists established ec50 for cisplatin in skov3 cell line, and it varied from 2 to 40 um. Apoptosis of hela cells induced by cisplatin and its mechanism. Gleevec sti571 inhibits lung cancer cell growth a549 and. However, in this publication there are some interesting data regarding that variation. Both cisplatin and complex 10d cause in hela cells characteristic for apoptosis morphological changes of cell nuclei and internucleosomal cleavage of dna. The a2780dr cell line is a cisplatinresistant variant of a2780. However, the resistant cell line was twofold more efficient at effluxing drug, which was associated with reduced total drug accumulation for equivalent. For cisplatin treatment, cells were cultured at 5 x 10 4 cellswell in a 6well plate in three replicates 48 hours prior to the addition of the previously determined ic 50 of cisplatin for each cell line in rpmi 1640 containing 10% fbs and 1% penicillinstreptomycin solution.
The study of cytotoxicity to glc4 and glc4 cddp cell lines showed similar ic50 values approximately 1. Cisplatin is particularly effective against testicular cancer. Cellid cisplatin contains a mixture of naturally occurring platinum isotopes, and is best detected in the 195 channel. The half maximal inhibitory concentration ic50 is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. The genomics of drug sensitivity in cancer project is a collaboration between the cancer genome project at the wellcome sanger institute uk and the center for molecular therapeutics, massachusetts general hospital cancer center usa. Ic 50 is a quantitative measure that indicates how much of a particular inhibitory substance e.
1500 102 1040 629 1276 425 187 1026 246 1322 569 132 1429 521 1247 697 905 1442 598 287 95 1248 1201 158 468 330 253 957 1254 472 937 1490 42 785 280 78 1242 1329 1019 967 1098 1004 397 368 1463