Tetrandrine (TET) has been reported to induce anti-cancer activity in many human cancer cells and also to inhibit cancer cell migration and invasion. However, there are no reports to show TET inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells. In this study, we investigated the anti-metastasis effects of TET on GBM 8401 cells in vitro. Under sub-lethal concentrations (from 1, 5 up to 10 μM), TET significantly inhibited cell mobility, migration and invasion of GBM 8401 cells that were assayed by wound healing and Transwell assays. Gelatin zymography assay showed that TET inhibited MMP-2 activity in GBM 8401 cells. Western blotting results indicated that TET inhibited several key metastasis-related proteins, such as p-EGFR (Tyr1068) , SOS-1, GRB2, Ras, p-AKT (Ser473) and p-AKT (Thr308) , NF-κB-p65, Snail, E-cadherin, N-cadherin, NF-κB, MMP-2 and MMP-9 that were significant reduction at 24 and 48 hours treatment by TET. TET reduced MAPK signaling associated proteins such as p-JNK1/2 and p-c-Jun in GBM 8401 cells. The electrophoretic mobility shift (EMSA) assay was used to investigate NF-κB and DNA binding was reduced by TET in a dose-dependently. Based on these findings, we suggested that TET could be used in anti-metastasis of human brain glioblastoma multiforme GBM 8401 cells in the future. K E Y W O R D S GBM 8401 cells, migration and invasion, MMP-2, NF-κB, Tetrandrine (TET) 1 | INTRODUCTION Malignant glioblastoma multiforme (GBM) are the most common and aggressive malignant primary brain tumor in humans and can be a fatal tumor because of difficulties in treating the related metastasis due to the high proliferation rate and invasiveness. 1-5 Currently, the treatment of GBM is the local irradiation, and conventional chemotherapy with temozolomide (TMZ) or surgical resection in combination with radiotherapy and chemotherapy but the median survival rate is only 8-15 months. 4-6 About 20% of patients after treated with TMZ have shown the clinical toxicity. 7 Due to the side effects of TMZ chemotherapy that leading to the limited efficiency. Thus, bases on the Yun-Lian Lin and Jing-Gung Chung contributed equally to this study.

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Generally, the NC format is the description for the positioning and/or the movement of its linear and rotary axes. As the multi-axis machine tools have a variety of configurations, their NC codes are not exchangeable. This issue leads to some inconvenience and confounding in the manufacturing processing schedule. Furthermore, when the specifications of tool such as length, diameter or shape are reset, the NC program must be regenerated accordingly. That is to say, the exchangeability of NC program among different five-axis machine configurations is an important issue in making better usage of industrial five-axis machine tools for efficient applications. An APT program records the tool path, tool vector and cutting information, etc. In particular, the recent development of APT format can provide the capability recording the motion posture of the tool such as the tool orientation, the position and its normal vector of the tool contact point. Therefore, it can solve the problems of the exchangeability for the different machine tools as well as the online resetting of tool specifications, even the tool posture. In this paper, a new method was proposed to interpret the APT code into tool movement data including toolpath, location, tool orientation, the contact point and its contact vector, etc., which can be applied to the conversion of different NC codes, or be connected to the controller of the machine tool so as to proceed the interpolation calculation for directly machining control. Moreover, the application scope can be extended to the verification of machining and to drive a virtual machine tool for previewing. Since the APT format varies according to different CAD/CAM systems, a common intermediate interchange standard (CMIS) was proposed, designed and verified in this paper as a feasible solution for the exchangeability of different APT formats. The process of the proposed method includes interpreting a variety of APT program into a common standard format, and then transforming this intermediate standard code into various NC programs for the corresponding machine configurations. An example was used to demonstrate how to convert an APT generated by CATIA software into intermediate code for a Table-Table five-axis machine tool with two rotary axes attached on table (XYZAC configuration). As the APT contains the definition of inclined plane, so the homogeneous coordinate transformation was adopted to transform the coordinate system of the inclined plane into the work coordinate system; it was further transformed into the corresponding NC program via an inverse kinematics transformation. This example has shown the feasibility of the method proposed. Moreover, the research can be applied not only to the exchangeability of different APT format but also to the other related applications such as the verification of machining error and the drive of virtual machine tool.

Machining processes on an inclined plane include mostly hole making, profiling, and pocketing. It comprises of 80% - 90% cutting process in five-axis machining and is therefore very important in multi-axis machining work. However, five-axis machining processes are normally difficult to introduce and to use because five-axis CAD/CAM and post-processor are normally demanded to generate five-axis NC program even though it is for the 2D contour machining on a plane with inclined angle. Therefore, this paper studies the inclined plane machining methods and extends traditional three-axis milling machining processes and methods so as to directly convert 2-1/2 and three-axis NC program into five-axis machining program to ease the application of five-axis machining processes. This study integrates the developed three-axis NC program interpreter, inclined plane coordinates transformation, and post-processor to simply the inclined plane NC programming. Two-dimensional NC program on a plane can be converted into five-axis NC program on the inclined-plane by the proposed methodology. Case study has been utilized to verify the utilization and correctness of the proposed methodology

The application of traditional three-axis milling machine center is very popular and the related application technology is also much matured resulting in mechanical components to be machined with good quality. Machine tool has therefore become an inevitable facility in precision manufacturing. Furthermore, the pursuit of higher precision machining has thus demanding five-axis machine tool to be adopted owing to its flexibility and capability in machining more precise mechanical components in shorter time. However, one of the key factors for the popularity in smooth introduction of five-axis machine tool would be based on a very user friendly learning and teaching environment. This is partly because two more rotational axes in a five-axis machine tool could generate very complex toolpath movement that is out of the imagination of a general operator. Furthermore, the price of an industrial five-axis machine tool is not normally affordable by an educational institute; to the worse, the maintenance cost is also very high. There is very high risk for a novice to collide during the learning process and this will generally cause big worry of a teacher. This paper aims for the development of a virtual machining center simulation system with switchable modular components to ease the learning process in getting acquainted with a five-axis machine tool. A five-axis machine tool consists generally of two modules: (1) CNC controller and Operation panel, and (2) machine tool hardware. The developed system will provide the novice with four CNC controller with operation human machine interface (HMI), and three typical types of five-axis machine tool, Head-Head (HH), Head-Table (HT), and Table-Table (TT), are also supported. The developed modularized and switchable machining center simulation system has been successfully developed and is very helpful to both learner and teacher