ABSTRACT
Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.
ABSTRACT
Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.
ABSTRACT
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent and antitumor potency. Particularly, compound was orally active and possessed excellent antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.
ABSTRACT
Fusarium solani strain ATLOY-8, a fungus that produces camptothecin (CPT) was isolated from Chonemorphafragrans (Moon) Alston. The process of optimization of the camptothecin yield was optimized by means of thetraditional methods and analytical tools. Using the Box–Behnken design (BBD) matrix at N = 17, three independentvariables were optimized designated using one factor at a time (OFAT) method, for improved CPT and biomassproduction. The BBD exhibited 1.4- and 1.2-fold increase of CPT production and biomass yield, respectively,compared to OFAT approach in the basal medium containing absolute ethanol (5%), glucose (1%), and precursors (acombination of tryptophan, geraniol, and tryptamine; 0.03%). Analysis of variance showed the elevated coefficient ofdetermination (R2) of 0.9751 and 0.9980, respectively, for CPT and biomass yielding at a significant level (p > 0.05).Three dimensional graphs revealed dependent synergy between two variables to improve the CPT and biomass yield
ABSTRACT
OBJECTIVE： To optimize the water extraction technology of Qiwei chanshen formula. METHODS： The content of polysaccharides from Gekko japonicus and Panax quinquefolium was determined by UV spectrophotometry， the contents of camptothecin from Camptotheca acuminata and ginsenoside Rb1 from P. quinquefolium were determined by HPLC. The extraction rate of above three components， dry extractum yield and HPLC fingerprint similarity were used as evaluation indicators； information entropy theory was used to determine the weight of each indicator so as to calculate comprehensive score. L9（34） orthogonal test was used to screen the optimal extraction technology of Qiwei chanshen formula with decoction time， water volume and decoction times as factors. Validation test was also performed. RESULTS： The optimal extraction technology included 10-fold water， decocting for 3 times， 1.0 h each time. The results of validation test showed that the average extraction rate of polysaccharide， camptothecin and ginsenoside Rb1 were 74.306％， 13.860％ and 52.958％， respectively. The average dry extractum yield was 16.150％， the average value of fingerprint similarity was 0.991 （all RSDs＜3.0％， n＝3）. CONCLUSIONS： The optimized extraction technology is reproducible， stable and feasible， providing reference for the subsequent development and industrial production of the formula.
ABSTRACT
Objective To evaluate transcather arterial chemoembolization (TACE) with hydroxycamptothecin combined with hepatectomy in treatment of primary liver cancer.Methods 64 primary liver cancer cases admitted and treated in Shanxi Provincial Cancer Hospital were divided into two groups with 32 cases in each.The control group were treated by surgery only and in the study group patients received TACE and hepatectomy.Results 0.5-year and 1-year recurrence rate in the study group were respectively 9.38％ and 28.13％,significantly lower than those in the control group.There was no significant difference in the 2-year recurrence rate between the two groups.0.5-year,1-year and 2-year survival rate in the study group were respectively 93.75％,84.38％ and 65.63％,significantly better than those in the control group.The AST and ALT were respectively (86 ±42)U/L,(96 ±55)U/L which were lower than those in the control group.The ALB and TBiL were respectively (32 ± 10) g/L and (24 ± 9) μmol/L,which were not significantly different with the control group.Conlunsion Hydroxycamptothecinbased TACE combined with hepatectomy is better than hepatectomy only for the treatment of primary liver cancer.
ABSTRACT
We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography (CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope (TEM) and further quantified by energy dispersive X-ray spectrometry (EDS) and inductively coupled plasma-optical emission spectrometers (ICP-OES). Due to gold's high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded gold atoms and clusters are expected to share the same biological fate as the camptothecin nanocrystals, reaching and accumulating in tumor site due to the enhanced permeation and retention (EPR) effect.
ABSTRACT
OBJECTIVE: To prepare and verify the anticancer drug camptothecin(CPT) and its inclusion complex with cucurbit[7]uril(CB[7]). METHODS: Camptothecin-cucurbit[7]uril inclusion complex was prepared by the lyophilization. The complex was characterized by fluorescence spectroscopy, Fourier transformation-infrared spectroscopy(FI-IR), differential scanning calorimetry(DSC), X-ray diffraction(XRD) and 1H-NMR. The dissolution properties of the inclusion complex was analyzed by ultraviolet spectrum. RESULTS: The formation of 1:2 complex with CB[7] in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constant was 3.95×1012 L2•mol-2.The stability and solubility of camptothecin was significantly improved after it was included with cucurbit[7]uril. CONCLUSION: Stable complex can be formed between camptothecin and cucurbit[7]uril,and the solubility of camptothecin is increased by CB[7] significantly.
ABSTRACT
Objective To study the antiviral effect and mechanism of camptothecin against HSV-1 in vitro. Methods Adding different concentration of camptothecin to the Vero cells infected by HSV-1, the measure of cytopathologic effects (CPE) was taken to evaluate the result of antiviral effect and mechanism of camptothecin. The median toxic concentration (TC50), median inhibitory concentration (IC50), and therapeutic index (TI) of camptothecin were calculated, and the affection of camptothecin on HSV-1 mRNA expression was examined through the method of RT-qPCR. Results TC50 of camptothecin was 2 153.44 nmol/L, IC50 was 43.01 nmol/L, and TI was 50.07. The results of RT-qPCR showed that camptothecin can significantly inhibit the gene transcription of HSV-1, UL12, UL42, UL54, and TK, and its inhibitory effect was in dose-dependence relationship with the concentration of camptothecin. Conclusion Camptothecin has an obvious antiviral effect on HSV-1 and can inhibit the transcription of HSV-1 genes such as UL12, UL42, UL54, and TK.
ABSTRACT
Objective To evaluate the effect of camptothecin on the autophagy of human primary keratinocytes (HPKs).Methods HPKs were isolated from foreskin tissues of healthy males by a two-step digestion method,and the third-passage cells were used for following experiments.These HPKs were randomly divided into several groups:experimental groups treated with camptothecin at concentrations of 200 nmol/L,2 and 6 μ mol/L separately,and a control group treated with 0.1％ dimethyl sulfoxide (DMSO).After 24-and 48-hour treatment,cell counting kit-8 (CCK-8)assay was conducted to estimate the proliferative activity of HPKs.Flow cytometry was performed to detect cell apoptosis after 24-hour treatment,and Western blot analysis to measure the expression of autophagy-associated proteins such as microtubule-associated protein 1 light chain-3 (LC3) and p62.Some other HPKs were treated with 2 μmol/L camptothecin for 24 hours.Indirect immunofluorescence assay was performed to observe changes in LC3 expression,and transmission electron microscopy to observe the ultrastructure of autophagosomes,so as to further validate the inductive effect of camptothecin on autophagy.Results The inhibitory effect of camptothecin on the proliferation of HPKs gradually increased along with the increase of camptothecin concentration,and there was a significant difference in the proliferation inhibition rates among the experimental groups and control group at 24 hours (F =152.9,P ＜ 0.01).Additionally,the proliferation inhibition rates were significantly higher in the 2-,6-μmol/L camptothecin groups than in the control group (t =12.09,18.76,both P ＜ 0.01),but there was no significantly difference between the 200-μmol/L camptothecin group and control group (t =2.24,P ＞ 0.05).At 48 hours,there was still a significant difference in the proliferation inhibition rates among the experimental groups and control group (F =123.8,P ＜ 0.01),and all the experimental groups showed increased proliferation inhibition rates compared with the control group (all P ＜ 0.01).At 24 hours,the cell apoptosis rates also significantly differed among the control group,200-nmoYL,2-μmol/L and 6-μmol/L camptothecin groups (2.30％ ± 1.68％,15.90％ ±2.14％,29.33％ ± 3.51％,35.28％ ± 3.05％,respectively;F =89.57,P ＜ 0.01),and all the three experimental groups showed higher cell apoptosis rates compared with the control group (all P ＜ 0.01).After 24-hour treatment with 2 or 6 μmol/L camptothecin,the protein expression of LC3]Ⅱ were significantly up-regulated,but the protein expression of p62 was significantly down-regulated.Indirect immunofluorescence assay showed that the percentage of autophagosome-positive cells was significantly higher in the 2-μmol/L camptothecin group than in the control group (60.16％ ± 8.78％ vs.38.96％ ±13.12％,t =3.003,P ＜ 0.05).After 24-hour treatment with 2 μmol/L camptothecin,autophagosomes and autolysosomes were observed in HPKs with a transmission electron microscope.Conclusion Camptothecin at concentrations of 2 and 6 μmol/L can increase the autophagy level in HPKs,meanwhile,inhibit cell proliferation and induce cell apoptosis.
ABSTRACT
To develop a cell-penetrating peptide with high membrane penetrating ability and effective antitumor activity, we designed and synthesized an analogue of penetratin, [Cys-CPT2,9] penetratin, by substitution of Gln2 and Asn9 with Cys-CPT. We investigated the transmembrane activity and antitumor activity of [Cys-CPT2,9] penetratin. The fluorescence intensity of [Cys-CPT2,9] penetratin in HeLa cells was observed by laser confocal microscopy and flow cytometry, and the cell uptake mechanism of [Cys-CPT2,9] penetratin was evaluated by using different endocytic inhibitors, finally the anti-tumor activity of [Cys-CPT2,9] penetratin was tested by MTT assay. The results showed that the membrane activity of [Cys-CPT2,9] penetratin was significantly enhanced in laser confocal microscopy and flow cytometry assay, and the intracellular fluorescence intensity was 5 times higher than penetratin. The cell uptake mechanism study of [Cys-CPT2,9] penetratin indicated that it mainly entered the cell through the clathrin and endocytosis. Moreover, [Cys-CPT2,9] penetratin exhibited anti-tumor activity against HeLa cells, and its inhibitory effect on cancer cells was stronger than CPT. [Cys-CPT2,9] penetratin is a new cell-penetrating peptide with high translocation ability, and has anti-tumor activity against HeLa cells.
ABSTRACT
Objective To evaluate effects of camptothecin on the autophagy of HaCaT cells.Methods Some cultured HaCaT cells were divided into several groups to be treated with camptothecin at concentrations of 5,10,25,50,100 and 200 nmol/L,and 0.1％ dimethyl sulfoxide (DMSO) (control group),respectively.Cell counting kit-8 (CCK-8) assay was conducted to estimate the proliferative activity of HaCaT cells after 24-and 48-hour treatment,flow cytometry to evaluate cell apoptosis after 24-hour treatment,and Western blot analysis to measure the expression of autophagy-related proteins microtubuleassociated protein 1 light chain 3 (LC3) and p62.Some HaCaT cells were divided into 2 groups to be treated with 10 nmol/L camptothecin and 0.1％ DMSO for 24 hours,respectively.Then,indirect immunofluorescence assay (IFA) was performed to determine the LC3 expression.Results Camptothecin at low concentrations of 5 and 10 nmol/L had no significant effects on the proliferation and apoptosis of HaCaT cells.Compared with the control group,the cellular proliferative rates were significantly inhibited by (31.23 ± 1.00)％,(54.21 ± 8.10)％ and (66.75 ± 10.70)％ in the 50-,100-and 200-nmol/L camptothecin groups after 24-hour treatment respectively,and by (25.81 ± 5.99)％,(44.35 ± 5.32)％,(65.81 ± 8.28)％ and (73.23 ± 9.59)％ in the 25-,50-,100-and 200-nmol/L camptothecin groups after 48-hour treatment respectively (all P ＜ 0.001).After 24-hour treatment,the apoptosis rates were significantly higher in the 50-,100-and 200-nnol/L camptothecin groups (14.46％ ± 2.38％,19.15％ ± 1.59％,29.88％ ± 1.37％,respectively) than in the control group (3.80％ ± 0.13％,all P ＜ 0.001).After 24-hour treatment with 5 and 10 nmol/L camptothecin,the protein expression of LC3 Ⅱ was significantly up-regulated,while p62 protein expression was significantly down-regulated:IFA showed that the percentage of autophagosome-positive cells was significantly higher in the 10-nmol/L camptothecin group than in the control group after 24-hour treatment (36.67％ ± 4.55％ vs.6.23％ ± 0.92％,t =6.546,P =0.003).Conclusions Camptothecin at low concentrations of 5 and 10 nmol/L can induce autophagy of HaCaT cells,but has no obvious effects on cell proliferation and apoptosis.Camptothecin at concentrations of 50,100 and 200 nmol/L can inhibit cell proliferation,promote cell apoptosis,and decrease autophagy levels.
ABSTRACT
A novel stability-indicating Reverse Phase High Pressure Liquid Chromatography (RP-HPLC-PDA) method was developed and validated for quantitative determination of Camptothecin (CPT) in bulk, formulation and in dissolution samples using Inertsil-C18 (250mm x 4.6mm, 5μm) column with mobile phase combination of 15mM Ammonium acetate and acetonitrile (60:40) at a flow rate of 1mL/min. Eluents were monitored at a wavelength of 254 nm with an injection volume of 20µL. CPT was completely degraded in oxidative and base hydrolysis conditions and around 37% in acidic conditions and no degradation of CPT was observed with thermal, thermal/humidity and photo conditions. CPT showed linearity over a concentration range of 2-10μg/mL with a regression coefficient (R2) of 0.994 and correlation coefficient (R) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) values for CPT were 0.025μg/mL and 0.077μg/mL respectively. The developed method was validated as per ICH guidelines. The method was also successfully applied to dissolution testing of controlled release formulation.
ABSTRACT
Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of DNA topoisomerase I and has applications in treating ovarian, small lung and refractory ovarian cancers. Stem wood tissue of Nothapodytes nimmoniana (Graham) Mabb. (family Icacinaceae) is one of the richest sources of CPT. Since there is no genomic or transcriptome data available for the species, the present work sequenced and analysed transcriptome of stem wood tissue on an Illumina platform. From a total of 77,55,978 reads, 9,187 transcripts were assembled with an average length of 255 bp. Functional annotation and categorization of these assembled transcripts unraveled the transcriptome architecture and also a total of 13 genes associated with CPT biosynthetic pathway were identified in the stem wood tissue. Four genes of the pathway were cloned to full length by RACE to validate the transcriptome data. Expression analysis of 13 genes associated with CPT biosynthetic pathway in 11 different tissues vis-à-vis CPT content analysis suggested an important role of NnPG10H, NnPSLS and NnPSTR genes in the biosynthesis of CPT. These results indicated that CPT might be synthesized in the leaves and then perhaps exported to stem wood tissue for storage.
ABSTRACT
OBJECTIVE: To investigate the effects of chrysin on the apoptosis induced by DNA damage antitumor drugs in hepatoma (Hep G2) cell lines, and its molecular mechanism. METHODS: Hep G2 cells were pretreated with chrysin for 2 h, then treated with cisplatin or camptothecin for 24 h. The morphologic changes were observed under inversed microscope and the cell viability was measured using MTT test. The proteins of caspase-3, PARP, Bcl-xL, xIAP and FLIP were determined by Western blot. RESULTS: Increases of cell death were observed in the combination of chrysin and cisplatin or camptothecin. There were significant differences in the cell viability not only between the combined treatment and the untreated control, but also between the combined treatment and chrysin alone, cisplatin alone or camptothecin alone. Chromatin condensation could be observed when the cells were stained by Hochest 33342 in the combination of chrysin and DNA damage antitumor drugs, and the apoptotic cells showed significant increase in the combination group compared with other groups(P < 0.05). The proproteins of caspase-3 and PARP degraded. The pan-caspase inhibitor z-VAD-fmk could inhibit the activation of caspase-3 and PARP induced by the combination of chrysin and cisplatin or camptothecin. The apoptosis inhibitory proteins, FLIP and xIAP which upregulated by cisplatin alone, could be downregulated by the cotreatment of chrysin and cisplatin; and Bcl-xL upregulated by camptothecin alone was downregulated by the combination of chrysin and camptothecin. CONCLUSION: Chrysin could sensitize the apoptosis induced by cisplatin and camptothecin, and the downregulation of apoptosis inhibitory proteins, which were regulated by NF-κB and augmented by cisplatin and camptothecin, played an important role in the sensitization.
ABSTRACT
objective To research whether the combination of chrysin and camptothecin can promote the apoptosis of human nasopharyngeal carcinoma cell line CNE2 and to explore the molecular mechanism of the combinative effect. Methods: CNE2 cells were pretreated with designed dose of chrysin (10|, 20, and 40 μmol/L) for 2 h, then treated with camptothecin (1 μg/mL) for 24 h. The morphologic changes were observed under inversed microscope and the cell viability was measured using MTT. The activity of caspase-3 and PARP, which was regarded as the protein marks of apoptosis, was determined by Western blotting. Then the cells were treated with chrysin for different time and the time course of apoptosis inhibitory protein, Bcl-xL was also detected using Western blotting. Results: Increases of cell death were observed in the group with combined chrysin and camptothecin, but no obvious cell death could be found in chrysin, camptothecin alone, and control groups; The data of cell viability supported this results; With the enhance of pretreatment dose of chrysin, the cell viability decreased. There were the significant differences between the combined groups and the control one (P<0.05), and between the combined groups and both the chrysin and camptothecin groups separately (P<0.05). Chromatin condensation, which was the indication of apoptosis, could be observed when the cells were stained with Hochest 33342; The proprotein of caspase-3 and PARP degraded and there were the dose-dependent and time-dependent effect. The pan-caspase inhibitor Z-VAD-fmk could inhibit the apoptosis of CNE2 cells which were treated with the combination of chrysin and camptothecin, according to the cell viability and the activation of caspase-3 and PARP; The time-dependent down-regulation in the apoptosis inhibitory protein Bcl-xL could be observed. Conclusion: The cotreatment of chrysin and camptothecin could promote the apoptosis of CNE2 and the down-regulation of apoptosis inhibitory protein Bcl-xL played an important role in the combinative effect.
ABSTRACT
Objective: Camptothecin (CPT) as a kind of poorly soluble drug was conducted micronization research. Methods: CPT micronized powder was prepared by emulsification method using emulsification machine and high pressure homogenizer. Moreover, single factor method was utilized to optimize. Dissolution and oral bioavailability study on CPT micronized powder prepared under the best emulsification conditions was conducted. Results: The best preparation conditions were as follows: The dosage of Tween-80 as the surfactant was 0.4%; The concentration of CPT in chloroform-methanol (8:2) mixed solution was 1 mg/mL; The volume ratio of water-organic phase was 7:3; The homogenate speed was 7 000 r/min for 11 min. The particle size of CPT micronized powder prepared under the optimized conditions was (165.6 ± 5.3) nm. The scanning electron microscopy (SEM) results showed that CPT micronized powder presented regular strip shape and uniform particle size. The dissolution study indicated that the solubility and dissolution rate of CPT micronized powder was increased by 1.36 and 4.09 times compared with the raw CPT powder. The results of oral bioavailability showed that compared with the raw CPT powder, the relative bioavailability of CPT micronized powder in mice was increased by 2.10 times. The results of gas chromatography showed that residual solvents in CPT micronized powder accorded with the standard of ICH. Conclusion: Solubility and dissolution rate of CPT are both improved since CPT micronized powder is prepared by emulsification method. So the oral bioavailability is also improved.
ABSTRACT
Objective To prepare a novel drug delivery system camptothecin loaded nanogel (CPT-PPO gel),and inves-tigate its contents,physical and chemical properties and in vitro transdermal permeability.Methods The solvent evaporation method was utilized to prepare core-shell nano-drug delivery systems (CPT-PLGA-PAMAM,CPT-PP),in which the Poly lac-tic-co-glycolic acid (PLGA ) was used to load camptothecin as the nucleus and the polyamidoamine (PAMAM ) G3.0 was wrapped in the surface of PLGA as the shell.Then the oleic acid (OA) was connected to CPT-PP to obtain the surface modified drug delivery system (CPT-PLGA-PAMAM OA,CPT-PPO).HPLC was used to determine the content of camptothecin in nanoparticles,transmission electron microscopy was applied to identify the nanoparticles morphology,and laser analyzer was used to determine the particle size.The hydroxypropyl methylcellulose (HPMC) was added as the base for the preparation of the nanogel (CPT-PPO gel) at last.The Franz-diffusion cell was used to determine the permeation rate of nanogel in vitro. Results The resulting CPT-PPO gel was stable at 4℃,the average particle size was (246.7 ± 5.4) nm and the encapsulation efficiency was up to (78.7 ± 6.9)%.Comparing to the normal gel,(CPT gel),the cumulative penetration amount and the re-tention amount in the skin of the nanogels (CPT-PPO gel,CPT-PP gel) were significant higher (P＜0.01),the retention and cumulative penetration amount of CPT-PPO gel was significant higher than that of CPT-PP gel (P＜0.05).Conclusion After modified by OA,CPT-PPO gel can increase the cumulated amount and absorption in skin and can be used as a carrier of CPT in the new formulation for topical treatment of psoriasis.
ABSTRACT
Objective To explore the efficacy and safety of irinotecan as neoadjuvant chemotherapy (INAC) plus radical surgery (RS) for cervical cancer.Methods According to International Federation of Gynecology and Obstetrics (FIGO),81 cases were divided into Ⅱ B,ⅡA,and Ⅰ B2 groups.According to the tests of UGT1A1 gene polymorphisms,we adjusted the injection dose of irinotecan.The parameters were analyzed,including the efficacy,operation time and bleeding volume,postoperative pathology,survival time,and adverse reactions.The articles on irinotecan or paclitaxel combined with cisplatin for neoadjuvant chemotherapy between 2005 and 2015 were collected,and compared.Results The effective rate of chemotherapy was 81.5％ (Ⅰ B2 group:85.7％;Ⅱ A group:83.3％;and ⅡB group:72.2％),operation time was (5.3 ± 1.1) h,and blood loss was (781 ± 361.7) ml.After chemotherapy,37 cases were delayed diarrhea,70 cases were nausea,48 cases were vomiting,and 40 cases were bone marrow suppression.The infiltration rate,operation time,and blood loss on Ⅱ B group was significantly higher than that on Ⅱ A and Ⅰ B2 groups(P ＜ 0.05),and there was no significant difference in the chemotherapy efficiency,invasion depth,lymphatic metastasis,survival time and adverse reactions(P ＞0.05).Compared to three articles,the total effective rate in this study was higher than that in previous studies,also in Ⅱ A and Ⅱ B group.Conclusions Irinotecan chemotherapy regimens combined with cisplatin is effective and well tolerated.It is worthy of popularization and application.Detection of UGT1A1 gene polymorphism has guiding significance for chemotherapy regimen on irinotecan combined with cisplatin.
ABSTRACT
Objective:To explore the effect of autophagy inhibitor 3-methyladenine(3-MA) on camptothecin(CPT)-induced Hela cell apoptosis.Methods:MTT assays were carried out to determine the optimal concentration and time of CPT on Hela cells and the effect of different drugs on Hela cell proliferation activity .After Hela cells were treated with different drugs ,the changes of autophagy marker protein( microtubule-associated protein 1 light chain 3,LC3),p62 and apoptosis-related protein were detected using Western blot and immunofluorescence ( IF) .DAPI ( nuclear ) staining was used to observe cell apoptosis rate .Results: In CPC-treated Hela cells,Hela cell proliferation activity declined dramatically ,and autophagy could be induced to occur .Compared with CPT group ,the cell proliferation activity was lower in CPT combined with 3-MA group,the level of autophagy decreased ,but the apoptosis rate significantly increased.Conclusion:CPT can induce autophagy while inducing Hela cell death .Hela cells chemosensitivity to CPT treatment can be enhanced by 3-MA inhibiting autophagy .