High dose Vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC.

Vitamin C (VitC) presents excellent anti-tumor effect for long time. Recently, high dose VitC achieved by intravenous administration manifests superior anti-tumor effect. However, the functions and detailed mechanisms of high dose VitC's role in cancer immunity are not fully understood. This study investigates the effect of high dose VitC on PD-L1 expression in triple negative breast cancer (TNBC) and the potential mechanism. Results showed VitC inhibited PD-L1 expression in breast cancer cell lines and enhanced anti-tumor effects of T cells. Furthermore, we found VitC inhibited PD-L1 transcription through ROS-pSTAT3 signal pathways. Consistent with in vitro results, in vivo study showed VitC suppressed tumor growth in immunocompetent mice and enhanced CD8+ T cells infiltration and function in tumor microenvironment. Our findings identify the effects of high dose VitC on PD-L1 expression and provide a rationale for the use of high dose VitC as immunomodulator for cancer therapy.

Saikosaponin-d Increases the Radiosensitivity of Hepatoma Cells by Adjusting Cell Autophagy.

Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.

Saikosaponin-d increases the radiosensitivity of smmc-7721 hepatocellular carcinoma cells by adjusting the g0/g1 and g2/m checkpoints of the cell cycle.

BACKGROUND: Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia. METHODS: Cell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively. RESULTS: Treatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia. CONCLUSION: SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.

[Absorption and distribution of nitrogen, phosphorus and potassium in Chrysanthemum morifolium].

OBJECTIVE: To study Chrysanthemum morifolium dry matter accumulation and absorption characteristics of nitrogen, phosphorus and potassium at different growth stages. METHOD: Through the field experiment and the sampling analysis, the absorbing capacity of nitrogen, phosphorus and potassium as well as the growth of plant at different growth stages in Ch. morifolium were analyzed. RESULT: The dry matter accumulation reached 70.4% of the total accumulation within 60-150 days after transplantation. Dry matter mainly distributed in leaf within 60 days after transplantation, the distribution ratio in the stem was higher than that in leaf within 60-150 days after transplantation, the highest distribution ratio was the flower, and the second was the root within 150-210 days after transplantation. The accumulative capacity of N, P and K by Ch. morifolium was lower within 45 days after transplantation, which only accounted for 16.14%, 13.39% and 10.19% of total absorptive capacity, respectively. But it increased rapidly within 45-150 days after transplantation, which accounted for 71.86%, 63.81% and 62.94% respectively. The nitrogen accumulation was slower, while the accumulation of phosphorus and potassium was increased rapidly, within 150-210 days after transplantation. The distribution ratio of nitrogen, phosphorus and potassium was different within different organs in different growth stages. The distribution ratio of nitrogen, phosphorus and potassium was mainly distributed in stem and leaf, within 150 days after transplantation, then transferring to the flower and root, the transferring efficiency was N > P > K. CONCLUSION: the absorption capacity of K was the highest, followed by N and P. The N : P205 : K2O ratio was 1 : 0.88 : 1.58. Correlation analysis showed that dry matter accumulation and nitrogen, phosphorus and potassium accumulation correlated positively. For producing 1g dry matter, Ch. morifolium needed to absorb 5.198 1 mg N, 4.329 5 mg P205 and 7.138 5 mg K20 from soil and fertilizer.

Clinical effects of lianbai liquid in prevention and treatment of dermal injury caused by radiotherapy.

OBJECTIVE: To observe the effect of Lianbai liquid in prevention and treatment of acute radiation dermal injury. METHOD: From May 2000 to December 2005, 126 cancer patients were randomly divided into a prevention group of 75 cases given externally topical application of Lianbai liquid since the first radiotherapy, and a control group I of 51 cases given only advice after radiotherapy; while the other 92 cancer patients who had already had grade III acute radiation-induced dermal injury were randomly divided into a treatment group of 54 cases treated by externally topical use of Lianbai liquid, and a control group II of 38 cases treated by topical use of norfloxacin. Clinical evaluation was carried out according to the CTC.V2.0 standard stipulated by NCI for classifying acute radiation dermal injury. RESULTS: The incidence of skin reaction was 32.0% in the prevention group and 92.2% in the control group I, with an obvious difference between the two groups (chi2=54.163, P<0.01). Mild radioactive reaction (grade I and II) was 28.0% (21/75) in the prevention group and 70.6% (36/51) in the control group I, with a remarkable difference between the two groups (chi2=22.226, P<0.01). The effective rate for grade III dermal injury was 92.6% (50/54) in the treatment group and 65.9% (25/38) in the control group II, with a remarkable difference between the two groups (chi2=6.018, P=0.024). The wound-healing time was 11.07+/-2.21 days in the treatment group and 18.08+/-1.76 days in the control group II, with a remarkable difference between the two groups (u=16.932, P<0.01). CONCLUSION: Lianbai liquid can effectively prevent the radiation dermatitis, and treat grade III acute radiation dermal injury with obvious curative effect.