[Effect of valproic acid on Expression of Bim gene and viability of ovarian cancer cell line A2780]

Background and Objective: Ovarian cancer is the fifth common cancer among women and the number of new cases is increasing. Valproic acid is a histone deacetylase inhibitor effectively used to treat epilepsy and bipolar disease. Recently, this compound has attracted attention as an anti-cancer agent. Bim is one of the most important genes of mitochondrial pathway of apoptosis, and it plays an important role in the biology of cancer. Expression of this gene is greatly reduced in ovarian cancer. This study was done to evaluate the effect of valproic acid on the viability of ovarian cancer cells, apoptosis and Bim gene expression in A2780 line

Methods: In this experimental study, the human ovarian cancer cells [A2780] were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated by various concentrations valproic acid [1-30 mM] and were incubated for 24, 48 and 72 hours. After the incubation of period, cell viability was investigated using MTT. Apoptosis was analyzed by flow-cytometry method in the cells were treated by valproic acid. The Real time PCR test was used to assess the effect of this drug on the expression of Bim gene

Results: The results of MTT assay showed that valproic acid reduced the viability of A2780 cells, and this effect was time and dose-dependent. The reduction of cell viability at 30 mM concentration and 72 hours after treatment, was maximum and statistically significant [P<0.05]. Exposure to valproic acid significantly increased the percentage of apoptotic cells [P<0.05]. Also, Valproic acid significantly increased the expression of Bim [P<0.05]

Conclusion: Valproic acid reduced viability in ovarian cancer cell line A2780. Valproic acid increased cell death by altering the expression of genes involved in apoptosis in ovarian cancer cell lineA2780

Association between BIM gene and glucocorticoid resistance in children with acute lymphoblastic leukemia / 中国当代儿科杂志

Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in childhood. Glucocorticoids are frequently used in the chemoradiotherapy regimen for ALL and can induce the apoptosis of ALL cells through several signaling pathways, but about 10% of ALL children have poor response to glucocorticoids. Studies have revealed that glucocorticoids induce the apoptosis of ALL cells by upregulating the expression of BIM gene, and BIM gene is associated with glucocorticoid resistance in childhood ALL. This article reviews the recent studies on glucocorticoid resistance in childhood ALL, especially the role of BIM and its expression products in this process.

Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

Effect of Foxo3a gene over-expression on the development of rat ovarian granulose cells and in prevention of cisplatin-induced ovarian damage in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of Foxo3a gene over-expression on the development of rat ovarian granulosa cells and in prevention of cisplatin-induced ovarian damage in rats.</p><p><b>METHODS</b>Rat ovarian granulose cells released mechanically from the ovaries were cultured in vitro and identified with HE staining and immunohistochemical staining for FSHR. A recombinant adenovirus carrying Foxo3a gene was constructed for infecting the granulose cells, and the cell growth and expressions of cyclin D1, p27, Bax, and Bim were detected; the cell apoptosis and cell cycle changes were detected using Hoechst/PI 33342 staining and flow cytometry, respectively. The transfected cells were challenged with cisplatin and the cell apoptosis was detected with flow cytometry.</p><p><b>RESULTS</b>Over 90% of the cultured cells survived and contained more than 95% ovarian granulose cells. Infection of the cells with the recombinant adenovirus resulted in over-expressions of Foxo3a at the mRNA and protein levels at 36 h and 48 h after the infection, respectively. The infected cells showed suppressed proliferation, increased apoptotic rate and cell cycle arrest in G1 phase with increased expressions of Bim, p27, and cyclin D1 but without significant changes in Bax expression. Cisplatin exposure caused a significantly higher apoptosis rate in the infected cells than in the control cells.</p><p><b>CONCLUSION</b>Over-expression of Foxo3a gene can promote granulose cell apoptosis by increasing Bim expression and cause cell cycle arrest in G1 phase by increasing cyclin D1 and p27 expressions, but can not prevent the toxic effects of cisplatin on ovarian granulosa cells.</p>

Threonine 32 (Thr32) of FoxO3 is critical for TGF-β-induced apoptosis via Bim in hepatocarcinoma cells

Transforming growth factor-β (TGF-β) exerts apoptotic effects on various types of malignant cells, including liver cancer cells. However, the precise mechanisms by which TGF-β induces apoptosis remain poorly known. In the present study, we have showed that threonine 32 (Thr32) residue of FoxO3 is critical for TGF-β to induce apoptosis via Bim in hepatocarcinoma Hep3B cells. Our data demonstrated that TGF-β induced FoxO3 activation through specific de-phosphorylation at Thr32. TGF-β-activated FoxO3 cooperated with Smad2/3 to mediate Bim up-regulation and apoptosis. FoxO3 (de)phosphorylation at Thr32 was regulated by casein kinase I-ε (CKI-ε). CKI inhibition by small molecule D4476 could abrogate TGF-β-induced FoxO/Smad activation, reverse Bim up-regulation, and block the sequential apoptosis. More importantly, the deregulated levels of CKI-ε and p32FoxO3 were found in human malignant liver tissues. Taken together, our findings suggest that there might be a CKI-FoxO/Smad-Bim engine in which Thr32 of FoxO3 is pivotal for TGF-β-induced apoptosis, making it a potential therapeutic target for liver cancer treatment.

Adenovirus mediated BIMS transfer induces growth supression and apoptosis in Raji lymphoma cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To transfer pro-apoptotic BIM directly into tumor cells bypass the complicated biological processes of BIM activation so as to reverse the chemoresistance of cancer cells.</p><p><b>METHODS</b>BIMS was specifically amplified from HL-60 cells by RT-PCR, confirmed to be correct by sequencing and cloned into shuttle vector pAdTrack-CMV carrying a green fluorescence protein gene to generate a recombinant plasmid pAdTrack-CMV-BIMS. This plasmid and adenovirus backbone plasmid pAdEasy-1 were linearized and electroporated into E.coli BJ5183 host bacteria to mediate homologous recombination. The positive clone was identified by restrict endonuclease digestion. The recombinant pAdEasy-CMV-BIMS was transferred into HEK293 cells for packaging and amplification. The successful construction of recombinant human BIMS adenovirus (Ad-BIMS) was demonstrated by Western blot. To test whether Ad-BIMS has the capability of inducing apoptosis of tumor cells, Ad-BIMS was used to infect GC resistant Burkitt lymphoma Raji cells.</p><p><b>RESULTS</b>After infected for 2-5 days, BIMS expression in Raji cells was detected by RT-PCR and Western blot. The significant growth retardation and apoptosis of Raji cells were also observed by MTT and flow cytometry.</p><p><b>CONCLUSION</b>These results indicated that BIMS might be a potential candidate of gene therapy for chemoresistant tumor cells.</p>

Involvement of Toll-like receptor 4 in apoptosis of hippocampal neurons through Akt/FoxO3a/Bim signaling pathways / 生理学报

The present study was to investigate whether Toll-like receptor 4 (TLR4)-mediated Akt/FoxO3a/Bim signaling pathway participated in lipopolysaccharide (LPS)-induced apoptosis in hippocampal neurons. The primarily cultured rat hippocampal neurons were treated with LPS, TLR4 antibody+LPS, and LY294002+LPS, respectively. Cell vitality was assayed by CCK-8. Expressions of p-Akt, Akt, p-FoxO3a, FoxO3a, Bim and active-Caspase-3 of each group were detected by Western blot analysis; the mRNA expression of Bim was detected by real-time quantitative PCR; FoxO3a nuclear translocation was detected by fluorescence microscope. The rate of cell apoptosis was assayed by flow cytometry. The results showed that cell vitality of hippocampal neurons decreased after being treated with LPS in a time-dependent way. Compared with the control group, the expressions of p-Akt and p-FoxO3a decreased significantly, FoxO3a translocated into the nucleus, meanwhile, the expression of Bim and active-Caspase-3, and the apoptotic ratio of hippocampal neurons increased in LPS treated neurons. Pretreatment with TLR4 antibody significantly blocked, while PI3K antagonist LY294002 further strengthened these changes induced by LPS. In conclusion, the present study suggests that Akt/FoxO3a/Bim signaling pathways mediated by TLR4 participate in the apoptotic processes of primarily cultured hippocampal neurons treated with LPS, and the activation of TLR4 causes neuronal apoptosis.

Role of BH3-only gene in the oxaliplatin-induced apoptosis of colon cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the role of BH3-only gene in oxaliplatin-induced apoptosis of human colon cancer cell line, and to explore the associated mechanisms.</p><p><b>METHODS</b>Two strains of human colon cancer cell line SW480 and HT29 were selected, and treated respectively with different concentrations of oxaliplatin (0.3, 0.6, 1.25, 2.5, 5, 10 and 20 mg/L). Cell growth and inhibition were detected by MTT method. Apoptosis was measured by flow cytometry. Bim and PUMA expressions were examined by fluorescence quantitative PCR.</p><p><b>RESULTS</b>After treatment of different oxaliplatin concentrations in human colon carcinoma cells SW480 line, the cell growth was inhibited in a dose-dependent manner, while Bim and PUMA expressions were significantly up-regulated. While HT29 cell lines received the same treatment, no obvious inhibition of cell growth and up-regulation of Bim and PUMA expression were found. When SW480 cells were exposed to 5 mg/L and 10 mg/L of oxaliplatin for 24 h, the early apoptotic rates were (4.87±0.55)% and (12.10±1.04)%; for 48 h, the early apoptotic rates were (11.47±0.85)% and (30.07±2.01)%; for 72 h, the early apoptotic rates were (28.99±2.12)% and (38.32±3.15)% respectively, which were all significantly higher than those in control group [(0.30±0.10)%, (0.40±0.10)% and (0.50±0.20)%, all P<0.01]. In HT29 cells, the differences of apoptotic rates between oxaliplatin treatment group and control group were not statistically significant (all P>0.05).</p><p><b>CONCLUSIONS</b>Oxaliplatin can inhibit colon cancer cell line SW480 growth and induce apoptosis. Induction of apoptosis of colon cancer cells by oxaliplatin may be associated with the up-regulation of BH3-only proteins, Bim and PUMA.</p>

Role of the FOXO3a transcription factor in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the role and mechanisms of FOXO3a nuclear translocation in neuronal apoptosis after hypoxia-ischemia (HI).</p><p><b>METHODS</b>One hundred and sixty 10-day-old Sprague-Dawly rats were randomly divided into two groups: HI and sham-operated. The right common carotid artery was ligated followed by hypoxia exposure for 2.5 hours in the HI group. The sham-operated group rats were not subjected to carotid artery ligation or hypoxia treatment. Rat cerebral cortex was collected at 0.5, 2, 4, 8 and 24 hours after hypoxia. Western blot was used to detect expression of total FOXO3a protein, pnuclear and cytoplasmic FOXO3a and Bim. TUNEL staining was used to detect apoptotic cells.</p><p><b>RESULTS</b>The nuclear protein of FOXO3a obviously increased from 0.5 to 24 hours after HI in a time-dependent manner compared with the sham-operated group (P<0.01). On the contrary, cytoplasmic protein evidently decreased from 0.5 to 24 hours in the HI group compared with the sham-operated group (P<0.01). Bim protein increased from 0.5 hour, peaked at 2 hours, started to decline at 4 hours (P<0.01), and returned to baseline level at 8 and 24 hours after HI in the HI group compared with the sham-operated group. TUNEL positive cells started to express at 4 hours, and peaked at 24 hours after HI (P<0.01). However, TUNEL positive cells were rarely found in the sham-operated group.</p><p><b>CONCLUSIONS</b>HI induces FOXO3a translocation from cytoplasm to nucleus, and enhances protein expression of its target gene Bim in the neonatal rat brain. The upregulation of Bim expression might be related to neuronal apoptosis.</p>

Relationship between PUMA and BIM expression in colorectal cancer and tumor invasion, metastasis and prognosis / 中华外科杂志

<p><b>OBJECTIVE</b>To study p53 up-regulated modulator of apoptosis (PUMA) and bcl-2 interacting mediator of cell death (BIM) of the BH3-only protein family expression in colorectal cancer tissues and its relationship with colorectal cancer invasion, metastasis and prognosis.</p><p><b>METHODS</b>Immunohistochemical staining (EnVision) was used to detect PUMA/BIM expression in 30 cases of normal mucosa, 30 cases of colorectal adenoma and 142 cases of colorectal cancer tissues.</p><p><b>RESULTS</b>PUMA in colorectal cancer tissues was positive expressed (82.4%), which was significantly lower than in the normal mucosa colorectal adenomas (96.7%) and normal mucosa tissues (96.7%) (both χ(2) = 3.93, P < 0.05). Positive expression rate of BIM in colorectal cancer tissues (62.7%) was significantly lower than that in colorectal adenomas and normal mucosa (96.7% and 90.0%) (χ(2) = 8.42 and 13.29, P < 0.01). PUMA and BIM in colorectal cancer tissues were positively correlated (r = 0.747, P = 0.000). PUMA expression was related to tumor differentiation (χ(2) = 11.87), invasion depth (χ(2) = 11.59), lymph node metastasis (χ(2) = 12.82), TNM stage (χ(2) = 33.47) and P-gp expression (χ(2) = 18.30), all P < 0.05, but not related to the patients' age, gender, tumor size, tumor histological type and GST-π expression (P > 0.05). BIM expression was related to tumor differentiation (χ(2) = 16.19), lymph node metastasis (χ(2) = 14.95), TNM stage (χ(2) = 52.66) and P-gp expression (χ(2) = 10.60) (P < 0.05), but not related to patients' age, sex, tumor size, tumor histological type, invasion depth and GST-π expression (P > 0.05). 1-, 3-, 5-year survival rates of the positive expression of PUMA/BIM in patients with colorectal cancer were significantly higher than that of PUMA/BIM in patients with negative expression (χ(2) = 6.10 and 27.6, P < 0.05). Cox multivariate analysis showed that lymph node metastasis (RR = 0.238), TNM stage (RR = 7.895), PUMA (RR = 1.691) and BIM (RR = 0.440) could be used as independent prognostic indicators (P < 0.05).</p><p><b>CONCLUSIONS</b>PUMA and BIM expressions in colorectal cancer are related to the tumor invasion, metastasis and prognosis. Low expressions of PUMA and BIM were related to the late period and poor prognosis of colorectal cancer patients.</p>

Expression of Bim, Bax and Bak in the process of gingipain-induced osteoblast apoptosis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To establish osteoblast apoptosis model induced by gingipains, and to examine the expression of pro-apoptotic protein Bcl-2 interacting mediator (Bim), Bcl-2 associated X protein (Bax) and Bcl-2 antagonist/killer (Bak).</p><p><b>METHODS</b>Gingipain and gingipain acticity were extracted and measured. Mouse osteoblast cell line MC3T3-E1 cells were cultured in the presence of 0.453, 0.906, 1.812 U/L gingipains for 0, 16, 24 and 48 h. Apoptosis was examined by 4',6-diamidino-2-phenylindole (DAPI) staining or annexin V/propidine iodide (PI) staining.Protein expression of Bim, Bax and Bak was determined by Western blotting after osteoblasts were cultured with 1.812 U/L gingipain for 0, 4, 8, 16, 24 and 48 h. Osteoblasts were cultured with 1.812 U/L gingipain which had been inhibited with N-alpha-tosyl L-lysyl-chlorom ethylketone (TLCK). Western blotting was used to detect Bim expression and DAPI staining to measure apoptosis.</p><p><b>RESULTS</b>Arginine-specific proteinases (Rgp) activity was (18.11 ± 2.11) U/L and specific proteinases (Kgp) was (1.02 ± 0.25) U/L. Percentage of osteoblast apoptosis induced by 1.812 U/L gingipain rose to (6.31 ± 0.37)% after 16 h, and reached (11.20 ± 0.35)% at 24 h and (10.80 ± 0.46)% after 48 h with DAPI staining. Annexin V/PI staining supported the result from DAPI staining.Bim protein level increased during osteoblast apoptosis, the relative fold rose to (0.31 ± 0.03) after 4 h (about 2 fold compared to control), peaking at 24 h (0.57 ± 0.05, 3-4 fold compared to control). Proteinase inhibitor TLCK effectively blocked the activity of gingipain and inhibited up-regulation of Bim induced by gingipains from (0.58 ± 0.04) to (0.14 ± 0.03). The percentage of osteoblast apoptosis decreased from (11.20 ± 0.35)% to (4.31 ± 0.38)% in the presence of TLCK. Expression of Bax remained unchanged when cells were cultured with or without gingipains. Bak was under the detectable level in MC3T3-E1.</p><p><b>CONCLUSIONS</b>1.812 U/L gingipains induced osteoblast apoptosis. Protein expression of Bim was up-regulated during cell apoptosis and was down-regulated when gingipain inhibited with TLCK, suggesting that Bim was involved in osteoblast apoptosis induced by gingipain. Inhibition of Bim protein expression protected osteoblast from apoptosis.</p>

Effects of arsenic trioxide combined with bortezomib on apoptosis of multiple myeloma cell line KM3 and its mechanisms / 中国实验血液学杂志

This study was purposed to investigate the effect of bortezomib (Bor) and arsenic trioxide (As(2)O(3)) combination on multiple myeloma cell line KM3 and its mechanisms. KM3 cells were cultured with different concentration of Bor or As(2)O(3) as well as both for a certain time. The cell proliferation was analysed by MTT assay and the concentration of 50% proliferation inhibition (IC(50)) was calculated. Early apoptosis and late apoptosis of KM3 cells were detected by Annexin-V-FITC Kit, and the change of transmembrane potential was measured by flow cytometry. mRNA of Caspase-3, Bim and Bcl-xL were detected by RT-PCR. The results showed that the proliferation inhibitory rate of KM3 cells treated by Bor plus As(2)O(3) was much higher than that of KM3 cells treated by Bor only for 72 h [ (27.64 ± 0.81)% vs (21.67 ± 2.20)%, P < 0.05]. There were more KM3 cells treated by Bor plus As(2)O(3) in early apoptosis at 48 h and late apoptosis at 72 h than that of KM3 cells treated only by Bor [ (53.20 ± 3.70)% vs (35.40 ± 2.58)%, P < 0.01; (63.96 ± 2.97)% vs (54.08 ± 3.76)%, P < 0.01]. Transmembrane potential (Δψm) of KM3 cells treated by Bor plus As(2)O(3) decreased more at 48 h, as compared with Bor alone. The expression levels of caspase-3 mRNA and Bim mRNA in KM3 cells treated with Bor plus As(2)O(3) were higher than that in KM3 cells treated with Bor alone. But the expression level of Bcl-xL mRNA was lower than that in KM3 cells treated with Bor alone. It is concluded that As(2)O(3) can enhance the apoptosis-inducing effect of Bor on multiple myeloma cell line KM3, which is associated with decreasing the expression of Bcl-xl mRNA and increasing the expression of Caspase-3 and Bim mRNA.

Role of dysregulation of Bim in resistance of melanoma cells to endoplasmic reticulum stress-induced apoptosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a model of ER stress-induced apoptosis with tunicamycin and to examine whether Bim is dysregulated and its potential role in resistance of melanoma cells to apoptosis under endoplasmic reticulum (ER) stress.</p><p><b>METHODS</b>A model of ER stress-induced apoptosis was established with tunicamycin. Apoptotic cells were quantitated using the annexin V/propidium iodide method by flow cytometry. Hoechst staining was also used to confirm the apoptotic cell death. Western blotting was used to measure the activation of caspase-3 and -9, and the expression of Bim, GRP78, CHOP, and Foxo1 at the protein level. The expression of Bim, CHOP and Foxo1 at the mRNA level was quantitated by qPCR. The siRNA technique was used to inhibit the expression of Bim.</p><p><b>RESULTS</b>Treatment of the melanoma cells with tunicamycin did not induce significant apoptosis and activation of caspase cascade, whereas it caused marked activation of caspase-3 and -9, and apoptosis in HEK293 cells which were used as a control. With exposure to tunicamycin (3 µmol/L) for 12, 24, 36 hours the Bim protein levels were not increased in Mel-RM and MM200 cells. Its mRNA levels were 0.37 ± 0.05, 0.13 ± 0.02 and 0.02 ± 0.01 in Mel-RM cells, while 0.41 ± 0.06, 0.16 ± 0.04 and 0.21 ± 0.03 in MM200 cells, respectively. The expression of Bim mRNA was significantly reduced compared with that in the control groups of the two cell lines (P < 0.01). siRNA knockdown of Bim protected HEK293 cells against activation of caspase-3. The cell apoptosis of Bim siRNA group was (5.69 ± 0.38)%, significantly lower than that of the siRNA control group (40.32 ± 1.64)% and blank control group (35.46 ± 2.01)% (P < 0.01). In the melanoma cells after exposure to tunicamycin (3 µmol/L) for 6, 12, 24, and 36 hours the transcription factor CHOP at mRNA level were significantly increased and the expressions at protein level were also up-regulated. The expressions of another transcription factor Foxo1 at mRNA level significantly decreased and the expressions at protein level were down-regulated, too.</p><p><b>CONCLUSIONS</b>The lack of Bim up-regulation contributes to the resistance of melanoma cells to ER stress-induced apoptosis and may be a mechanism by which melanoma cells adapt to ER stress conditions. Transcription factors CHOP and Foxo1 may be responsible for the dysregulation of Bim in melanoma cells upon ER stress.</p>

Early apoptosis of HL-60 cells induced by anti-CD44 McAb A3D8 inhibiting ERK1/2-upregulated Bim expression / 中国实验血液学杂志

This study was aimed to investigate the effects of anti-CD44 mAb A3D8 on proliferation and apoptosis of AML cells, to explore the mechanism of ERK1/2 and Bim in this process. Effect of the anti-CD44 mAb A3D8 on the HL-60 cell proliferation was assayed with MTT method, the change of mitochondrial transmembrane potential of HL-60 cells was analyzed by flow cytometry. The mRNA expression of Bim was determined by real-time quantitative RT-PCR. Western blot was used to detect the protein expression of p-ERK1/2. The results showed that mAb A3D8 could remarkably inhibit the proliferation capacity of the HL-60 cells in a dosage- and time-dependent ways. The mitochondrial transmembrane potential in HL-60 cells treated with A3D8 (3.0 µg/ml) was significantly decreased as compared with the control cells. Furthermore, the mRNA expression of Bim was much higher than that in controls. Expression of the p-ERK was much lower than that of the controls. It is concluded that anti-CD44 mAb A3D8 can inhibit the proliferation and induce the apoptosis of HL-60 cells, mechanism of which is enhancing the expression of Bim via inhibiting p-ERK1/2.

Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells / 癌症

Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.

Down-regulation of CD147 expression induces SiHa cell apoptosis through the Bcl-2 pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in SiHa cell apoptosis after inhibition of CD147 expression.</p><p><b>METHODS</b>RNA interference (RNAi) technique was used to down-regulate CD147 expression in SiHa cells, and RT-PCR and Western blotting were used to detect expression of CD147, Bcl-2, Bim and caspase-3; the percentage of cell apoptosis were detected by flow cytometry.</p><p><b>RESULTS</b>SiRNA sequence 1, 2 inhibited CD147 expression in SiHa cells effectively (P<0.05), resulting also in down-regulated expression of Bcl-2 (P<0.05) and up-regulated expression of caspase-3 and Bim(P<0.05). The percentage of apoptotic cells increased significantly, and early apoptosis was the most obvious in the cells (P<0.05).</p><p><b>CONCLUSION</b>Silencing of CD147 expression induces SiHa cell apoptosis partially through the Bcl-2 pathway .</p>