Acetylation- and ubiquitination-regulated SFMBT2 acts as a tumor suppressor in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (RCC) is the most common kidney tumor. The analysis from medical database showed that Scm-like with four MBT domains protein 2 (SFMBT2) was decreased in advanced clear cell RCC cases, and its downregulation was associated with the poor prognosis. This study aims to investigate the role of SFMBT2 in clear cell RCC. METHODS: The expression of SFMBT2 in clear cell RCC specimens were determined by immunohistochemistry staining and western blot. The overexpression and knockdown of SFMBT2 was realized by infection of lentivirus loaded with SFMBT2 coding sequence or silencing fragment in 786-O and 769-P cells, and its effects on proliferation and metastasis were assessed by MTT, colony formation, flow cytometry, wound healing, transwell assay, xenograft and metastasis experiments in nude mice. The interaction of SFMBT2 with histone deacetylase 3 (HDAC3) and seven in absentia homolog 1 (SIAH1) was confirmed by co-immunoprecipitation. RESULTS: In our study, SFMBT2 exhibited lower expression in clear cell RCC specimens with advanced stages than those with early stages. Overexpression of SFMBT2 inhibited the growth and metastasis of clear cell RCC cells, 786-O and 769-P, in vitro and in vivo, and its silencing displayed opposites effects. HDAC3 led to deacetylation of SFMBT2, and the HDAC3 inhibitor-induced acetylation prevented SFMBT2 from SIAH1-mediated ubiquitination modification and proteasome degradation. K687 in SFMBT2 protein molecule may be the key site for acetylation and ubiquitination. CONCLUSIONS: SFMBT2 exerted an anti-tumor role in clear cell RCC cells, and HDAC3-mediated deacetylation promoted SIAH1-controlled ubiquitination of SFMBT2. SFMBT2 may be considered as a novel clinical diagnostic marker and/or therapeutic target of clear cell RCC, and crosstalk between its post-translational modifications may provide novel insights for agent development.

Atomic layer deposited TiO2 nanofilm on titanium implant for reduced the release of particles.

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants. Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs. Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects. Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

Temperature-sensitive hydrogel releasing pectolinarin facilitate scarless wound healing.

The dressing that promotes scarless healing is essential for both normal function and aesthetics after a wound. With a deeper understanding of the mechanisms involved in scar formation during the wound healing process, the ideal dressing becomes clearer and more promising. For instance, the yes-associated transcriptional regulator (YAP) has been extensively studied as a key gene involved in regulating scar formation. However, there has been limited attention given to pectolinarin, a natural flavonoid that may exhibit strong binding affinity to YAP, in the context of scarless healing. In this study, we successfully developed a temperature-sensitive Pluronic@F-127 hydrogel as a platform for delivering pectolinarin to promote scarless wound healing. The bioactive pectolinarin was released from the hydrogel, effectively enhancing endothelial cell migration, proliferation and the expression of angiogenesis-related genes. Additionally, a concentration of 20 µg/mL of pectolinarin demonstrated remarkable antioxidant ability, capable of counteracting the detrimental effects of reactive oxygen species (ROS). Our results from rat wound healing models demonstrated that the hydrogel accelerated wound healing, promoting re-epithelialization and facilitating skin appendage regeneration. Furthermore, we discovered that a concentration of 50 µg/mL of pectolinarin incorporated to the hydrogel exhibited the most favourable outcomes in terms of promoting wound healing and minimizing scar formation. Overall, our study highlights that the significant potential of locally released pectolinarin might substantially inhibit YAP and promoting scarless wound healing.

Cellular Uptake of Engineered Extracellular Vesicles: Biomechanisms, Engineered Strategies, and Disease Treatment.

Extracellular vesicles (EVs), lipid-enclosed nanosized membrane vesicles, are regarded as new vehicles and therapeutic agents in intercellular communication. During internal circulation, if EVs are not effectively taken up by recipient cells, they will be cleared as "cellular waste" and unable to deliver therapeutic components. It can be seen that cells uptake EVs are the prerequisite premise for sharing intercellular biological information. However, natural EVs have a low rate of absorption by their recipient cells, off-target delivery, and rapid clearance from circulation, which seriously reduces the utilization rate. Affecting the uptake rate of EVs through engineering technologies is essential for therapeutic applications. Engineering strategies for customizing EV uptake can potentially overcome these limitations and enable desirable therapeutic uses of EVs. In this review, the mechanism and influencing factors of natural EV uptake will be described in detail. Targeting each EV uptake mechanism, the strategies of engineered EVs and their application in diseases will be emphatically discussed. Finally, the future challenges and perspectives of engineered EVs are presented multidimensionally.

Effects of gut microbiota on prostatic cancer: a two-sample Mendelian randomization study.

Aim: Recent observational and small-sample case-control studies have shown a relationship between gut microbiota composition and prostatic cancer (PCa). Nevertheless, the causal association between gut microbiota and PCa is still unclear. Herein, we used the Mendelian randomization (MR) method to explore the potential causal relationship between gut microbiota and PCa. Methods: In this two-sample MR study, data were extracted from the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium (n = 14,306) and the Dutch Microbiome Project (n = 8,208). Summary statistics for PCa were obtained from the FinnGen consortium release data (n = 95,213). Inverse variance weighted (IVW), MR-Egger, strength test (F), and MR-PRESSO were used to examine the potential causal association between gut microbiota and PCa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. Results: IVW estimates suggested that the relative abundance of Akkermansia muciniphila (odds ratio [OR] = 0.7926, 95% confidence interval [CI]: 0.6655-0.9440) and Bacteroides salyersiae (OR = 0.9023, 95% CI: 0.8262-0.9853) were negatively associated with the odds of PCa, while that of Eubacterium biforme (OR = 1.1629, 95% CI: 1.0110-1.3376) was positively associated with the odds of PCa. In addition, we explored these relationships among patients without other cancers and similarly found that the relative abundance of Akkermansia muciniphila, Bacteroides salyersiae, and Eubacterium biforme were linked to PCa (all P < 0.05). Conclusion: Gut microbiota potentially influenced the occurrence of PCa. Our findings may provide some new ideas for researching the methods of PCa prevention. In addition, further studies are needed to explore the causal association and specific underlying mechanisms between gut microbiota and PCa.

The induction of ferroptosis by KLF11/NCOA4 axis: the inhibitory role in clear cell renal cell carcinoma.

Ferroptosis is a form of cell death and has great potential application in the treatment of many cancers, including clear cell renal cell carcinoma (ccRCC). Herein, we identified the essential roles of Krüppel-like factor 11 (KLF11) in suppressing the progression of ccRCC. By analyzing mRNA expression data from the Gene Expression Omnibus (GEO) database, we found that KLF11 was a significantly downregulated gene in ccRCC tissues. The results of subsequent functional assays verified that KLF11 played an antiproliferative role in ccRCC cells and xenograft tumors. Furthermore, gene set enrichment analysis indicated that ferroptosis was involved in ccRCC development, and correlation analysis revealed that KLF11 was positively related to ferroptosis drivers. We also found that KLF11 promoted ferroptosis in ccRCC by downregulating the protein expression of ferritin, system xc (-) cystine/glutamate antiporter (xCT), and glutathione peroxidase 4 (GPX4), acting as the inhibitory factors of ferroptosis and increasing the intracellular levels of lipid reactive oxygen species (ROS). As a transcriptional regulator, KLF11 significantly increased the promoter activity of nuclear receptor coactivator 4 (NCOA4), a gene significantly downregulated in ccRCC and whose low expression is associated with poor survival. The characteristics of ccRCC cells caused by KLF11 overexpression were reversed after NCOA4 silencing. In summary, the present study suggests that KLF11 suppresses the progression of ccRCC by increasing NCOA4 transcription. Therefore, the KLF11/NCOA4 axis may serve as a novel therapeutic target for human ccRCC.

Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures.

The emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes.

Melatonin pretreatment on exosomes: Heterogeneity, therapeutic effects, and usage.

The therapeutic outcomes of exosome-based therapies have greatly exceeded initial expectations in many clinically intractable diseases due to the safety, low toxicity, and immunogenicity of exosomes, but the production of the exosomes is a bottleneck for wide use. To increase the yield of the exosomes, various solutions have been tried, such as hypoxia, extracellular acidic pH, etc. With a limited number of cells or exosomes, an alternative approach has been developed to improve the efficacy of exosomes through cell pretreatment recently. Melatonin is synthesized from tryptophan and secreted in the pineal gland, presenting a protective effect in pathological conditions. As a new pretreatment method, melatonin can effectively enhance the antioxidant, anti-inflammatory, and anti-apoptotic function of exosomes in chronic kidney disease, diabetic wound healing, and ischemia-reperfusion treatments. However, the current use of melatonin pretreatment varies widely. Here, we discuss the effects of melatonin pretreatment on the heterogeneity of exosomes based on the role of melatonin and further speculate on the possible mechanisms. Finally, the therapeutic use of exosomes and the usage of melatonin pretreatment are described.

Nanoengineering facilitating the target mission: targeted extracellular vesicles delivery systems design.

Precision medicine has put forward the proposition of "precision targeting" for modern drug delivery systems. Inspired by techniques from biology, pharmaceutical sciences, and nanoengineering, numerous targeted drug delivery systems have been developed in recent decades. But the large-scale applications of these systems are limited due to unsatisfactory targeting efficiency, cytotoxicity, easy removability, and instability. As such, the natural endogenous cargo delivery vehicle-extracellular vesicles (EVs)-have sparked significant interest for its unique inherent targeting properties, biocompatibility, transmembrane ability, and circulatory stability. The membranes of EVs are enriched for receptors or ligands that interact with target cells, which endows them with inherent targeting mission. However, most of the natural therapeutic EVs face the fate of being cleared by macrophages, resulting in off-target. Therefore, the specificity of natural EVs delivery systems urgently needs to be further improved. In this review, we comprehensively summarize the inherent homing mechanisms of EVs and the effects of the donor cell source and administration route on targeting specificity. We then go over nanoengineering techniques that modify EVs for improving specific targeting, such as source cell alteration and modification of EVs surface. We also highlight the auxiliary strategies to enhance specificity by changing the external environment, such as magnetic and photothermal. Furthermore, contemporary issues such as the lack of a gold standard for assessing targeting efficiency are discussed. This review will provide new insights into the development of precision medicine delivery systems.

Exosomes-mediated transfer of long noncoding RNA LINC01133 represses bladder cancer progression via regulating the Wnt signaling pathway.

Bladder cancer (BC), as one of the most common malignant cancers of the urinary system, has a high incidence and mortality rates. Recently, increasing studies have indicated that exosomes can mediate cellular communication in assorted cancers, including BC. Long noncoding RNAs (lncRNAs) have also been confirmed to take part in the regulation of many cancers. Long intergenic non-protein coding RNA 1133 (LINC01133) is an lncRNA and its roles in several cancers have been revealed. However, the functions of exosomes and LINC01133 in BC are still not elucidated. In our research, functional assays were conducted to evaluate the function of LINC01133, as well as the influence of exosomes and LINC01133 on BC cells. Western blot assay, immunofluorescence assay, electron microscope, and nanoparticle tracking analysis were applied for detecting the characteristics of exosomes. Bioinformatics tools and quantitative reverse-transcription polymerase chain reaction were performed to test the expression of LINC01133 in BC cells and exosomes of the immortalized human uroepithelial cell line (SV-HUC-1). Luciferase reporter assay was performed to measure the activity of the Wnt pathway. We discovered that LINC01133 expression was high in exosomes of SV-HUC-1 and low in that of BC cells. Additionally, exosomes restrained cell viability, proliferation, migration, and invasion. Similarly, LINC01133 exerted the same function on BC cells. In addition, the Wnt signaling pathway could be inactivated by LINC01133. Finally, in vivo experiments demonstrated that cell growth could be suppressed by overexpressed LINC01133. In short, exosomes-mediated transfer of lncRNA LINC01133 repressed BC progression via regulating the Wnt signaling pathway.

MicroRNA-1298-5p inhibits cell proliferation and the invasiveness of bladder cancer cells via down-regulation of connexin 43.

MicroRNA (miR)-1298 is widely down-regulated in a variety of malignant tumors, which facilitates cell proliferation, invasiveness, and migration. However, the specific biological function of miR-1298 in bladder cancer (BC) is still unknown. Connexin 43 (Cx43) is often up-regulated in tumors. Identifying miRNAs that target Cx43 in the setting of BC will help to develop Cx43-based therapies for BC. In this study, the results demonstrated that the expression levels of miR-1298 and Cx43 were significantly down-regulated and up-regulated, respectively, in BC tissues. Overexpression of miR-1298 inhibited cell proliferation, migration, and invasiveness in two BC cell lines as determined using MTT assays, cell cycle assays, colony formation assays, Transwell assays, gelatin zymography, and Western blot. In addition, we found that miR-1298 decreased Cx43 expression by directly targeting the 3'-UTR. Further, we observed that the promotion of BC cell proliferation, migration, and invasiveness from Cx43 on could be partially attenuated by overexpressing miR-1298. Moreover, the protein expression of p-ERK was ameliorated after transfection with overexpressed-miR-1298. Knockdown of Cx43 reversed the promotion of cell migration and invasiveness due to decreased expression of miR-1298. All of the data from our study indicate that miR-1298 could be a diagnostic marker of BC and a potential therapeutic agent via inhibiting Cx43.

Long non-coding RNA AFAP1-AS1 promotes proliferation and invasion in prostate cancer via targeting miR-512-3p.

BACKGROUND (OBJECTIVE): In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. METHODS: RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. RESULTS: AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. CONCLUSION: AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.

Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis.

Background: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) have been the first-line treatments for advanced or metastatic urothelial carcinoma (AMUC). However, their effects are unsatisfactory, and more drugs and regimens still need to be explored. Objective: We aimed to comprehensively compare all possible regimens with GC or MVAC in randomized controlled trials (RCTs) by network meta-analysis. Methods: We searched the PubMed, Embase, and Cochrane databases for RCTs that evaluated regimens compared to GC or MVAC on AMUC patients. The major outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). A network meta-analysis was used to assess the effectiveness and safety of the included treatment regimens, and the regimens were then clustered by the average linkage method. Results: A total of 19 trials that assessed 3,363 AMUC patients were included. For PFS, paclitaxel plus GC (PGC) was significantly superior to GC (log hazard ratio (HR): -0.16; 95% confidence interval (CI): -0.32, 0.00) with a moderate level of reliability. However, there was no significant difference between PGC and MVAC (log HR: -0.03; 95% CI: -0.27, 0.20). For OS, PGC was significantly superior to GC (log HR:-0.17; 95% CI: -0.33, -0.00) with a moderate reliability level but not significantly different from MVAC (log HR: -0.10; 95% CI: -0.35, 0.15). Analysis of ORR showed that PGC was superior to MVAC (log odds ratio (OR): 0.59; 95% CI: 0.02, 1.16) with a low reliability level and GC (log OR: 0.41; 95% CI: 0.12, 0.71) with a moderate reliability level. In the cluster results, PGC and sorafenib plus GC (GCS) exhibited relative advantages in efficiency, followed by MVAC and apatorsen plus GC (GCA); however, PGC, gemcitabine plus carboplatin (GP), and MVAC had more serious side effects. Conclusions: In our analysis, PGC was superior to MVAC and GC in only the ORR results and superior to GC in the OS and PFS results but was not significantly different from MVAC. More individualized therapies with targeted drugs need to be studied.

miR-492 Promotes Cancer Progression by Targeting GJB4 and Is a Novel Biomarker for Bladder Cancer.

BACKGROUND: Bladder cancer is the most common urinary system malignancy in the United States and is characterized by its diverse prognosis and high recurrence rate. However, the molecular mechanisms underlying its progression remain unknown. Accumulating evidence suggests a critical role for miRNAs in bladder cancer progression. METHODS AND RESULTS: In this study, we found that miR-492 expression levels were significantly higher in bladder cancer tissue and the serum of bladder cancer patients by bioinformatics analysis and a panel of clinical samples. The results of receiver operating characteristic curve analysis suggested the potential diagnostic value of serum miR-492 for bladder cancer. In vitro and in vivo functional assays showed that knockdown of miR-492 suppressed proliferation and metastasis of bladder cancer cells. Gap junction beta-4 protein was predicted to be a direct target of miR-492, which was validated using a luciferase reporter assay. Further cellular functional assays showed that suppression of miR-492 abrogated bladder cancer cell proliferation and metastasis by targeting gap junction beta-4 protein. CONCLUSION: miR-492 promotes cancer progression by targeting GJB4 and is a novel biomarker for bladder cancer.

Collagen Type VI Alpha 3 Chain Promotes Epithelial-Mesenchymal Transition in Bladder Cancer Cells via Transforming Growth Factor ß (TGF-ß)/Smad Pathway.

BACKGROUND Collagen type VI alpha 3 chain (COL6A3) has been proven to be a biomarker in the occurrence and development of bladder cancer, which is the most common malignant tumor in the urinary system. This study aimed to explore the effect and molecular mechanism of COL6A3 on EMT in vitro induced by TGF-ß/Smad in bladder carcinoma. MATERIAL AND METHODS There were 42 patients included in the Kaplan-Meier survival analysis. A cell counting kit-8 (CCK-8) assay and an angiogenesis assay were used to measure cell proliferation and tube formation, respectively. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qPCR) were conducted for the proteins and mRNAs expression. RESULTS COL6A3 was highly expressed in tissues and cells of bladder cancer. COL6A3 silencing could inhibit the cell proliferation and angiopoiesis. In addition, COL6A3 silencing obviously suppressed the levels of matrix metalloproteinase-2 (MMP2), Matrix metalloproteinase-9 (MMP9), and vimentin. On the contrary, the levels of epithelium-specific cell-cell adhesion molecule (E-cadherin) and tumor inhibitor of metalloproteinase-1 (TIMP-1) were significantly increased. Furthermore, we found that COL6A3 silencing reduced the activity of p-Smad2, p-Smad3, and transforming growth factor ß (TGF-ß). CONCLUSIONS COL6A3 could influence the viability and angiogenesis of bladder cancer cells. COL6A3 may have a certain relationship with the TGF-ß/Smad-induced EMT process.

Laparoscopic ultrasonography: The wave of the future in renal cell carcinoma?

Laparoscopic or robotic surgery is the main method of treating renal cell carcinoma (RCC). Laparoscopic surgery can accurately target lesions and shorten patient recovery time. Renal endogenous tumors or inferior vena cava tumor thrombi are very difficult to remove using the laparoscopic approach. The emergence of laparoscopic ultrasonography (LUS) has solved this problem. LUS can assist in the detection of tumor boundaries and the extent of tumor thrombi. The lack of tactile feedback may hinder the development of laparoscopic surgery for the treatment of renal cancer. LUS has become an important tool that has improved the rates of successful surgery. LUS is applied in not only early and locally advanced RCC treatment but also in monitoring ablation therapy, testing renal blood perfusion, and exposing renal pedicles. Sonographic techniques used for LUS include initial B-mode, Doppler, and contrast-enhanced ultrasound (CEUS). Contrast agents applied for CEUS do not induce nephrotoxicity and can display renal perfusion more accurately than the regular color Doppler ultrasound. According to current literature, LUS is a promising technique for the treatment of RCC, especially for endogenous RCC or RCC with thrombosis, and for monitoring the effectiveness of radiofrequency ablation, although further well-designed studies are warranted.

Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer.

It has been shown that chemotherapy has limited antitumor activity against advanced urothelial bladder cancer (UBC). Consequently, there is an urgent need to develop effective therapeutic methods for patients with advanced UBC. In the present study, the inhibitory effects of lentinan alone, gemcitabine alone, or lentinan combined with gemcitabine on the proliferation of the UBC cell line, T24, were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, annexin V fluorescein isothiocyanate/propidium iodide staining, and flow cytometry were used to determine the proliferation and apoptosis of T24 cells in each treatment group. Survival-related protein expression was analyzed by western blotting. Increased concentrations of lentinan, or lentinan combined with gemcitabine, positively correlated with decreased T24 cell proliferation. Lentinan combined with gemcitabine chemotherapy significantly inhibited UBC cell proliferation. Gemcitabine has the ability to induce T24 cell apoptosis, and this effect is enhanced when it is combined with lentinan.