Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

Sen-Ling Feng,Hai-Bin Luo,Liang Cai,Jie Zhang,Dan Wang,Ying-Jiang Chen,Huan-Xing Zhan,Zhi-Hong Jiang,Ying Xie 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinicalcancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediatedby ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrateswere carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. Theexpressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cellxenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation ofABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPaseand reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 bindingsite which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 anddocetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizingeffect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXTtreatment significantly suppressed the growth of drug-resistant tumors without increase in toxicitywhen compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvantchemotherapy, which encourages further pharmacokinetic and clinical studies.

Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

Feng, Sen-Ling,Luo, Hai-Bin,Cai, Liang,Zhang, Jie,Wang, Dan,Chen, Ying-Jiang,Zhan, Huan-Xing,Jiang, Zhi-Hong,Xie, Ying The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

Optimal Timing of Radiotherapy with Alternating/Sequential Radio-Chemotherapy for Limited-stage Small Cell Lung Cancer

Wang, Li-Jie,Liu, Xiu-Ju,Guan, Yan,Zhang, Chu-Feng,Wang, Peng,Li, Yan,Guo, Qi-Sen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Objective: To investigate the optimal timing of radiotherapy with alternating/sequential radio-chemotherapy for limited-stage small cell lung cancer (LS-SCLC). Methods: 91 patients with LS-SCLC were retrospectively analyzed and divided into two groups according to the number of chemotherapy cycles before radiotherapy. If the patient received radiotherapy after 3 cycles or fewer cycles of chemotherapy, classification was into the early group, if not, into the late group. All patients received 6 cycles of standard chemotherapy (EP/EC) and conventional radiotherapy (56 gy~ 60 gy/28 f ~30 f). Results: The response rate (RR) of the early and late groups were 85.7% and 81.6%, respectively, with no significant difference (p>0.05). In contrast, the progression-free survival (PFS) in the early group was better than that in the late group (11.8 months vs 9.86 months), and the difference was significant (p<0.05). There was no significant difference between two groups in adverse reactions, which gastrointestinal irritation and bone marrow suppression being the most common (p>0.05). Conclusions: Radiotherapy after 3 cycles or fewer cycles of chemotherapy does not bring significant benefits for RR of patients with LS-SCLC, but it could significantly prolong their PFS without increase in adverse reactions.

Prostate-specific Antigen Velocity (PSAV) and PSAV per Initial Volume (PSAVD) for Early Detection of Prostate Cancer in Chinese Men

Zheng, Xiang-Yi,Zhang, Peng,Xie, Li-Ping,You, Qi-Han,Cai, Bo-Sen,Qin, Jie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Aim: To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men. Methods: Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis. Results: Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0ng/mL-10.0ng was 73.7% and 70.7%, respectively. Conclusions: The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.

Nanofiber Induced Silk Fibroin Nanofiber/Silk Fibroin (SFNF/SF) Fibrous Scaffolds for 3D Cell Culture

Shiyang Chen,Tongda Lei,Yunrui Zhang,Huancheng Wu,Sen He,Wei Liu,Jie Fan,Yong Liu 한국섬유공학회 2023 Fibers and polymers Vol.24 No.2

Fibrous 3D scaffold with small fiber diameter has the similar topographic and structural characteristics of native extracellularmatrix (ECM), which provides the beneficial microenvironment for cell adhesion, growth, migration, proliferation. However,the pore structure of the biopolymer scaffold is crucial for cell regulation and tissue regeneration in practical application. Inthis report, we proposed a nanofiber induced silk fibroin nanofibers/silk fibroin (SFNF/SF) fibrous scaffold with homogeneousmicron pores using fast freeze-drying technology under -196 °C. The physical, chemical and biological performance of thescaffold was investigated. Ethanol post treatment of the scaffold led to the conformation transition of silk fibroin from randomcoil (silk I) to beta-sheet (silk II) and increase of the crystallinity of the scaffold, which greatly improved the stability of thescaffold in water. Scaffolds made from 2 to 6% SFNF/SF solution with SFNF/SF ratio ranging from 1:1 to 1:8 exhibited threedimensional (3D) fibrous structure with porosity of 80–85% and pore size ranging from 5 to 15 μm due to the entanglementof the nanofibers. And the fibrous structure of the scaffolds can be adjusted by controlling the concentration of the SFNF/SF solution and the SFNF/SF ratio. Cell culture suggested that the 3D fibrous network structure with micron pores showedadvantages for cell migration comparing with the lamella structure scaffold. After 7 day’s culture, cells migrated to about240 μm inside the 6% 1:1 scaffold, while only about 160 μm inside the 6% 1:16 scaffold. The nanofiber induced micro porousSFNF/SF scaffolds by fast freeze-drying technology is potential for preparation of micron porous scaffold.

Effects of co-ion initial concentration ratio on removal of Pb2+ from aqueous solution by modified sugarcane bagasse

Jing Zhu,Jun-xia Yu,Jia-dong Chen,Jie-sen Zhang,Jia-qi Tang,Yuan-lai Xu,Yue-fei Zhang,Ru-an Chi 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.6

A modified sugarcane bagasse (SCB) fixed bed column was used to remove Pb2+ from aqueous solution. To determine the optimal condition for Pb2+ separation, Ca2+ was chosen as the model interfering ion, and effects of Ca2+ and Pb2+ initial concentration ratio (C0 Ca : C0 Pb) on the adsorption of Pb2+ were investigated. Results showed that adsorption amount ratio of Ca2+ and Pb2+ (qe Ca : qe Pb) had a good linear relationship with C0 Ca : C0 Pb. Mass ratio of Pb2+ absorbed on the modified SCB was higher than 95% at C0 Ca : C0 Pb<1.95, illustrating that Pb2+ could be selectively removed from aqueous solution. To verify that, simulated waste water containing co-ions of K+, Na+, Cd2+ and Ca2+ was treated, and results showed that the equilibrium amount of Pb2+, K+, Na+, Cd2+ and Ca2+ adsorbed was 134.14, 0.083, 0.058, 1.28, and 1.28mg g−1, respectively, demonstrating that the modified SCB could be used to remove Pb2+ from aqueous solution in the investigated range.

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody

Wu Hao,Wei Guoli,Luo Lixia,Li Lingchang,Gao Yibo,Tan Xiaobin,Wang Sen,Chang Haoxiao,Liu Yuxi,Wei Yingjie,Song Jie,Zhang Zhenhai,Huo Jiege 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological.Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment.The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.