Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia.

BACKGROUND: Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. METHODS: Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. RESULTS: The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). CONCLUSION: When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS.

Tegillarca granosa extract Haishengsu inhibits the expression of P-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells.

This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosaL., on a drug resistant leukemia cell line. Cultured K562/Adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 microg/mL, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and Bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P < 0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 microg/mL HSS group (14.8%) was lower than in the control (16.9%, P < 0.05) and the 10 microg/mL HSS group (7.3%, P < 0.05), but it was similar to the HSS 20 microg/mL group (10.7%, P > 0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing Bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P < 0.05). We conclude that HSS induces apoptosis of the Adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in Bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to Adriamycin and potentially enhance the therapeutic effects.

Effect of haishengsu as an adjunct therapy for patients with advanced renal cell cancer: a randomized and placebo-controlled clinical trial.

OBJECTIVE: The purpose of this study was to investigate the effect of Haishengsu, an extract from Tegillarca L. granosa, on the effects and side-effects of immunotherapy in patients with advanced renal cell cancer. METHODS: Fifty-five (55) patients with renal cell cancer were randomly divided into a Haishengsu group (n = 27, 2.4 mg, intravenously for 15 days) and a control group (n = 28). All patients were also treated with interleukin-2, interferon-alpha, and fluorouracil. RESULTS: In the Haishengsu group, the prevalence of gastrointestinal reactions to the immunotherapy was lower than in the control group (18.5% versus 64.3%, p < 0.01). In comparison with the control group, more patients from the Haishengsu group had increased food intake (74.1% versus 14.3%, p < 0.01), weight gain (77.8% versus 10.7%, p < 0.01) or an increase in Karnofsky Performance Status score (55.6% versus 17.9%, p < 0.01). The remission rate of cancer in the Haishengsu group was higher than in the control group (51.9% and 21.4%, p < 0.01). CONCLUSIONS: Addition of Haishengsu to the conventional immunotherapy is associated with an increased remission rate in patients with advanced renal cell cancer. Haishengsu was also associated with a reduced rate of gastrointestinal side-effects from the immunotherapeutic agents, and an improvement in the physical functionality of the patients.

Effect of a seashell protein Haishengsu on the immunological function of mice with Ehrlich ascites tumor.

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100 mg/kg, i.v., respectively), cyclophosphamide (10 mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100 mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P < 0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8 +/- 1.2, 16.9 +/- 3.9 and 25.3 +/- 2.9, respectively), was greater than in the control (7.3 +/- 1.4), or the cyclophosphamide group (0.33 +/- 0.4) (all P < 0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P < 0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor.

Antitumor effect of the seashell protein Haishengsu on Ehrlich ascites tumor: an experimental study.

The aim of the study was to investigate the in vivo effect of the seashell protein Haishengsu (HSS) on Ehrlich ascites tumor. Mice were inoculated with Ehrlich ascites tumor cells and randomly divided into three HSS groups and a control group. The survival times in the three HSS-treated groups was longer than in the control (P < 0.01) and the increased life span in the high-dose HSS group was greater than in the lower-dose groups (P < 0.05). In comparison with control group, the mice receiving pretreatment of HSS had longer survival times and greater life spans following inoculation of the ascites tumor (P < 0.05). HSS therefore prolongs survival times and increases the life spans of mice bearing Ehrlich ascites tumor. Pretreatment with HSS also diminishes the detrimental effect of Ehrlich ascites tumor on the prognosis of these animals.

Effect of Haishengsu on transplanted K562 and drug-resistant K562/ADM tumors: an experimental study.

PURPOSE: To evaluate the effect of Haishengsu (HSS) on transplanted K562 and drug-resistant K562/ADM tumors. METHODS: Mice were inoculated subcutaneously with K562 and K562/ADM cells, respectively. Tumour-bearing animals were divided into HSS, adriamycin, combination therapy (adriamycin plus HSS) and placebo groups. The anti-tumour effect was assessed by tumour growth curve and tumour inhibitory rate (IR). RESULTS: In animals inoculated with K562 cells, the inhibitory rates of high (1800mg/kg) and medium (900mg/kg ) dose HSS groups were 100% and 96.4%, respectively, which was higher than that in the adriamycin (88.9%) or the combination therapy groups (85.8%, P < 0.05). The inhibitory rate in the low-dose HSS group (53.4%) was lower than in all other groups (P < 0.01). In mice inoculated with K562/ADM cells, the inhibitory rates in the high, medium and low dose HSS groups were 100%, 95.9%, and 44.1%, respectively. In the adriamycin group, the inhibitory rate was 23.07%, which was lower than in the HSS group (P < 0.01). Pathological examination of tumour tissues from HSS-treated animals showed extensive necrosis and bleeding. CONCLUSIONS: Haishengsu inhibits the growth of transplanted K562 tumours in mice. It is also effective in suppressing the growth of drug-resistant K562/ADM tumors in this animal model.