Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma

Pan, P.,Y. Wu,Z.Y. Guo,R. Wang,Y.J. Wang,Y.F. Yuan. Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma. J Ethnopharmacol, 2012. 143(2):680-685.

C57BL/6 mice with Lewis lung carcinoma were divided into four groups: the control group (C), cisplatin group (1 mg/kg, DDP), low KLT group (6.25 ml/kg body weight [L]), and high KLT group (12.5 ml/kg body weight [H]). T cell proliferation was determined by the MTT assay. Nuclear factor-kappa B (NF-κB), inhibitor kappa B alpha (IκBα), IκB kinase (IKK) and epidermal growth factor receptor (EGFR) levels were measured by western blotting. An enzyme-linked immunosorbent assay was used to analyze the expression of interleukin-2 (IL-2). Intraperitoneal KLT significantly inhibited the growth of Lewis lung carcinoma, and the spleen index was significantly higher in the L and H groups than in the C group. KLT stimulated T cell proliferation in a dose-dependent manner. Treatment with KLT at either 6.25 or 12.5 ml/kg decreased the level of NF-κB in the nucleus in a dose-dependent manner, and KLT markedly decreased the expression of IκBα, IKK and EGFR in the cytoplasm of tumor cells and overall. IL-2 was significantly increased in the supernatant of splenocytes in the H group. These results demonstrate that KLT has pronounced antitumor and immunostimulatory activities in C57BL/6 mice with Lewis lung carcinoma. These may affect the regulation of NF-κB/IκB expression, in addition to cytokines such as IL-2 and EGFR. Further work needs to investigate the relevant signaling pathway effects, but our findings suggest that KLT may be a promising antitumor drug for clinical use.

Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes

Shan, S.J.,T. Xiao,J. Chen,S.L. Geng,C.P. Li,X. Xu,Y. Hong,C. Ji,Y. Guo,H. Wei,W. Liu,D. Li,H.D. Chen. Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med, 2012. 29(4):625-629.

Ultraviolet (UV) radiation plays an important role in the pathogenesis of skin photoaging. Depending on the wavelength of UV, the epidermis is affected primarily by UVB. One major characteristic of photoaging is the dehydration of the skin. Membrane-inserted water channels (aquaporins) are involved in this process. In this study we demonstrated that UVB radiation induced aquaporin-3 (AQP3) down-regulation in cultured human skin keratinocytes. Kanglaite is a mixture consisting of extractions of Coix Seed, which is an effective anti-neoplastic agent and can inhibit the activities of protein kinase C and NF-κB. We demonstrated that Kanglaite inhibited UVB-induced AQP3 down-regulation of cultured human skin keratinocytes. Our findings provide a potential new agent for anti-photoaging.

Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2

Lu, Y.,L.Q. Wu,Q. Dong,C.S. Li. Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2. Hepatobiliary Pancreat Dis Int, 2009. 8(3):267-272.

KLT at different concentrations was used for the treatment of hepatocellular carcinoma cells in vitro, respectively. The proliferation inhibitory rate was evaluated by MTT assay, induction of cell apoptosis rate and the protein levels of Fas and Fas ligand (FasL) were determined by flow cytometry (FCM), and the expression of Fas and FasL mRNA was detected by real-time fluorescent quantitative RT-PCR. KLT produced an obvious time and dose-dependent inhibitory effect on HepG2 cells, and marked apoptosis was detected by FCM. The protein of Fas increased by 11.01%, 18.71%, 28.71% and 37.15%; the protein of FasL increased by 1.49%, 1.91%, 3.27% and 3.38% in comparison with the control (P<0.05). Real-time fluorescent quantitative RT-PCR showed that treating HepG2 cells with KLT caused the upregulation of Fas and FasL mRNA. KLT inhibits HepG2 growth by inducing apoptosis, which may be mediated through activation of the Fas/FasL pathway.

The effect of kanglaite injection (KLT) on the proliferation and telomerase activity of rat mesangial cells

Hu, Y.,H. Liang,W.K. Gong,Z.F. Xu,Q.L. Zou. The effect of kanglaite injection (KLT) on the proliferation and telomerase activity of rat mesangial cells. Zhongguo Zhong Yao Za Zhi, 2005. 30(6):450-453.

MTT, telomere repeat amplification protocal (TRAP), ELISA, PAGE and silver-stain were applied to detect the growth rate and telomerase activity of mesengial cell (MC) after stimulation of Kang Lai Te (KLT) and IL-1. The growth rate of MC was enhanced by IL-1 stimulation, which was accompanied with a redection of the activity of telomerase. Adversely, the growth rate of MC was reduced by KLT, which was accompanied with an enhancement of activity of telomerase. Moreover, the growth rate of MC and the activity of telomerase were both inhibited by the combinative use of IL-1 and KLT without any influence from the sequence of their administration. KLT could inhibit proliferation and telomerase activity of MC with or without pre-stimulation with IL-1. KLT might be useful to prevent and treat glomerular nephritis related to MC proliferation.

Study on the gene expression patterns of Kanglaite in anti-lung metastasis of LA795 mouse

Wu, Y., Y. Yang,D. Wu. Study on the gene expression patterns of Kanglaite in anti-lung metastasis of LA795 mouse. Zhongguo Fei Ai Za Zhi, 2003. 6(6):473-476.

To screen the differential expression genes of Kanglaite in anti-tumor metastasis mRNA was extracted and purified from the lung of the mouse with LA795 lung metastasis, and hybridized respectively on 4 096-gene chip. cDNA microarray was scanned for the fluorescent signals and analyzing difference expression. Twenty-seven differential expressed genes were obtained. Among these genes, 25 were up-regulated and 2 were down-regulated. Twelve of them were Mus musculus cDNA clone. Six genes related with genesis, development and metastasis of tumor. cDNA microarray for analysis of gene expression patterns is a powerful method to identify differential expressed genes. In this study, 6 genes are thought to be associated genes of Kanglaite in anti-tumor metastasis.

Kanglaite for Treating Advanced Non-small-cell Lung Cancer: A Systematic Review

Source: Zhu, L.,Z. Yang,S. Wang,Y. Tang. [Kanglaite for Treating Advanced Non-small-cell Lung Cancer: A Systematic Review.]. Zhongguo Fei Ai Za Zhi, 2009. 12(3):208-215.

To review the effectiveness and safety of Kanglaite for treating advanced non-small-cell lung cancer authors searched the Cochrane Library, Pubmed, Embase, Cancerlit, CBM, CNKI and VIP. Manual and additional search were also conducted. All randomized controlled trials/quasi-RCT comparing Kanglaite with other lung cancer treatments were included. Two reviewers independently performed data extraction and appraised the publications using the Juni instrument, disagreements were resolved by consensus. Double data were entered and analyzed by RevMan 4.2 software are by Cochrane Collaboration. Sixteen reports were included in the meta-analysis. The quality of 16 studies was low. Pooling data of 5 studies indicated that the effect of Kanglaite+NP (Vinorelbine+Cisplatin) was better than NP with RR 1.46, 95% Confidence Interval 1.13 to 1.91. Pooling data of 3 studies of MVP (Mitomycin+Vindsine+ Cisplatin) plus Kanglaite indicated that the effect was better with RR 1.84, 95%CI 1.22 to 2.76. Pooling data of 2 studies showed that the effect of GP (Gemcitabine+Cisplatin) plus Kanglaite was better than GP with RR 1.63, 95%CI 1.09 to 2.43. Fourteen studies revealed that Kanglaite may reduce the side-effect induced by regular treatment. Ten studies showed regular treatment plus Kanglaite can stabilite/improve quality of life.

Anticancer Chinese herbal Kanglaite (KLT)
Invented by famous pharmacological Prof. Li Dapeng , Kanglaite Injection (KLT) has been listed by the Chinese government as a "State Basic Drug", a "State Basic Medical Insurance Drug" and a "State Key New Drug".

Based on pre-clinical studies at John Hopkins University, USA, tumor-inhibitive rate of KLT on transplanted breast carcinoma induced by cell strain MDA-MB-231 was over 50%.
KLT could inhibit the expression of COX2 of the strain in vitro and act as an inhibitor of fatty acid synthase.
The broad ranged basic studies in China also revealed KLT different mechanisms such as inducing cancer cell apoptosis, inhibiting angiogenesis, reversing MDR and regulating gene expression of Fas/Apo-1 and Bcl-2.
Both Chinese and overseas clinical experiences have shown that KLT has proven effect in the treatment of cancers mainly at sites of lung, breast, liver, nasopharynx, esophagus, stomach, pancreas, kidney, colon-rectum, ovary and prostate. This agent is also applied in the treatment of malignant lymphoma and acute leukemia. KLT has brought great benefits to over 500,000 cancer patients in more than 2,000 big or medium hospitals in China since 1997.
The year 1995 witnessed KLT patent certificates granted from China and USA, In August 1997 the phase III clinical study was successfully completed and the injection was officially launched in China after final approval from the Ministry of Public Health.
FDA approved KLT clinical study in USA in March 2001 and the phase I study at Huntsman Cancer Institute, Salt Lake City, Utah was satisfactorily completed which laid a solid foundation for forthcoming clinical trials. Russian Federation approved KLT clinical study in January 2002 and the phase II study was smoothly ended in April 2003 with inspiring outcomes. In December 2003 the registration certificate was issued from Russian Ministry of Health and KLT has been marketed in Russia from 2005 with positive response. Currently an international multi-center randomized clinical study on KLT combined with first line chemotherapeutic drugs in the treatment of non-small cell lung cancer (NSCLC) is in progress.
Doctors in America carried out a phase 1 study of Kanglaite in 2003. They gave it to 16 people who had different types of cancer including lung, prostate and oesophageal cancers. The results showed people did not have many side effects but the effect on their cancer varied. Some people showed no response, and their cancers continued to grow. But in others, the cancer stopped growing for a few months.
Standard treatment course for KLT is 200 ml (2 bottles) per day via intravenous drip x 42 days (84 bottles). There is a break for 4-5 days after 21 days. And clinical experiences in China and Russia suggest 2 treatment courses for those with late stage advanced and metastatic tumors for better therapeutic effect and evident prolongation of life.

Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer
Qi F, Li A, Inagaki Y, Gao J, et al. Biosci Trends. 2010 Dec;4(6):297-307.

Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo- or radio-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by chemo- and radio-therapy. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides evidence for use of Chinese herbal medicines as adjuvant cancer treatment during chemo- or radio-therapy.
First, Chinese herbal medicines (e.g. Astragalus, Turmeric, Ginseng, TJ-41, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used by cancer patients for treating the cancer and/or reducing the toxicity induced by chemo- or radio-therapy are discussed. Preclinical and clinical studies have shown that these Chinese herbal medicines possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo- and radio-therapeutics, improving an organism's immune system function, and lessening the damage caused by chemo- and radio-therapeutics.
Second, clinical trials of Chinese herbal medicines as adjuvant cancer treatment are reviewed. By reducing side effects and complications during chemo- and radio-therapy, these Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving respiratory tract infections and gastrointestinal side effects including diarrhea, nausea, and vomiting, protecting liver function, and even ameliorating the symptoms of cachexia.
This review should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs.

Clinical safety and efficacy of Kanglaite® (Coix Seed Oil) injection combined with chemotherapy in treating patients with gastric cancer
Zhan YP, Huang XE, Cao J, et al. Asian Pac J Cancer Prev. 2012;13(10):5319-21.

To observe efficacy and side effects, as well as the impact on quality of life, of Kanglaite® (Coix Seed Oil) injections combined with chemotherapy in the treatment of advanced gastric cancer patiensts. A consecutive cohort of 60 patients were divided into two groups:the experimental group receiving Kanglaite® Injection combined with chemotherapy and the control group with chemotherapy alone. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated.
The response rate and KPS score of experimental group were significantly improved as compared with those of the control group(P< 0.05). In addition, gastrointestinal reactions and bone marrow suppression were significantly lower than in the control group(P< 0.05).
Kanglaite ® Injection enhanced efficacy and reduced the side effects of chemotherapy, improving quality of life of gastric cancer patients; use of Kanglaite® injections deserves to be further investigated in randomized control clinical trails.

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